American cutaneous leishmaniasis (ACL) is caused by several Leishmania species. It is more prevalent in tropical and subtropical regions of the world. This disease is highly endemic in Brazil, where it is considered an important health problem and where around 40,000 cases have been reported in 2002 alone (Desjeux, 2004). The development of a safe and effective vaccine still remains the most promising approach to prevent ACL (Desjeux, 1996; Kedzierski et al., 2006).Mayrink and collaborators developed and evaluated ACL vaccine candidates composed by killed promastigotes of Leishmania (Leishmania) amazonensis (Marzochi et al., 1998, De Luca et al., 2001; Mayrink et al., 2002; Armijos et al., 2004; Vélez et al., 2005). The main problem observed in the most recent studies using the vaccine was its low immunogenicity. Particularly, it was observed that after vaccination of volunteers, 30% of subjects showed no sign of protection when using the Montenegro skin test (MST) as immunological marker (i.e. their MST response was negative).Trace elements, such as copper, iron, selenium and zinc, can influence the innate and adaptive immunity; by modifying these immune cells activities (natural killer, macrophages, neutrophils and lymphocytes) and cytokines production (Erickson et al., 2000; Mocchegiani et al., 2000). Several studies have recently shown that the levels of these trace elements can change with the different clinical presentations of ACL and the others infectious process (Faryadi et al., 2003; Koçygit et al., 1998; Koçygit et al., 1999; Van Weyenbergh et al., 2004). But there are no data on the influence of the trace elements in the immune response induced by vaccination against ACL.Thus, the aim of this study presented here was to investigate the association of those trace elements and the immune response induced by vaccination against ACL, and whether this could explain the varying degree of responsiveness observed in some of the ACL vaccine trials.This experimental double-blind study was performed on a sub sample (n= 172) of the trial?s vaccinated subject group in Caratinga, Minas Gerais. Sixty days after vaccination, a new MST was applied to subjects. They were divided in two groups, in according with the MST response, those that had a negative (n=97) and positive (n=75) MST. The MST was positive when the induration?s diameter was > 5mm. In both groups? anthropometrics measures and blood samples were obtained. The trace elements were determinate by inductively coupled plasma atomic emission spectrometry (ICP-OES) (i.e. copper, iron and zinc) or by flux injection coupled hydride generation atomic absorption spectrometry (FIAS MHS) (i.e. selenium). All assays were performed in the metallic trace laboratory of CETEC, in two clean area ISO 7 and laminar airflow ISO 5 class cabinets using validated methods.The groups were composed by low (G0), normal (GI) and high (GII) serum levels of each trace element according to reference values. For statistical analysis purposes the subjects with a positive MST were classified into four groups, corresponding to the four quartiles of the observed diameter size distribution of positive MST respondents (i.e. 5 to 8 mm; 8.1 to 9 mm; 9.1 to 12 mm; > 12 mm).Among the subjects that had a positive MST response, the mean diameter was 10.35 ± 4.64 mm (mean ± SD). For all tested subjects the mean serum levels of copper, iron, selenium and zinc were 1433.7 ± 665.7 µg/L (mean ± SD; n = 171), 1431.6 ± 791.5 µg/ L (mean ± SD; n = 144), 88.6 ± 39.0 µg/L (mean ± SD; n = 157) and 999.2 ± 365.7 µg/L (mean ± SD; n = 171), respectively.The logarithm (log) MST diameter was significantly higher for subjects in GII (0.66 ± 0.53 mm) than G0/I (0.38 ± 0.51 mm) to selenium (p = 0.021). To zinc, the log MST diameter was significantly lower for subjects in GII (0.23 ± 0.43 mm) than in G0/I (0.48 ± 0.53 mm) (p = 0.033). No significant difference in log MST diameter was observed in copper and iron levels between GII and G0/I subject groups. The selenium levels also differed with the quartiles of the MST diameters of individuals testing positive (p = 0.019), with a tendency of increasing selenium serum levels associated with increasing MST diameter.Serum levels of zinc are associated to lower response induced by vaccine against ACL, available by MST. But the serum levels of selenium was associated an improvement of cellular response induced by vaccine against ACL.Future immunological and biochemical studies of vaccinated subjects that would be given selenium supplementation could improve our understanding about the relevance of this trace element for vaccine immunogenicity. Analyses will have to be adjusted for these levels, so that estimates of vaccine immunogenicity, evaluated by skin test, and protection can be rigorously estimated as well as compared between different studies.