This is a Phase 2B double-blind placebo-controlled crossover study evaluating the efficacy of intravenous fosaprepitant for chemotherapy-induced nausea and vomiting in patients undergoing high-dose interleukin-2 (HD IL-2) therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course) for metastatic melanoma and metastatic renal cell carcinoma. A total of 22 subjects will be enrolled in the study. On study entry, patients will be randomized to receive either IV fosaprepitant (150 mg on Day 1, Day 3, or Day 5) or matched placebo during first admission of HD IL-2 therapy (cycle 1). All subjects will crossover and receive the opposite treatment during cycle 2. All patients will receive ondansetron 24 mg by mouth daily per standard protocol every 24 hours during Days 1-5 of admission starting 30 minutes prior to first dose of HD IL-2. During the treatment phase, subjects will receive Patients will receive IV fosaprepitant 30 minutes before first dose of HD IL-2 therapy and every 48 hours until completion of HD IL-2 therapy. Upon study entry, the subjects will be given a dairy to report episodes of vomiting, use of rescue therapy, and nausea assessments using the 1-100 scale within the visual analogue scale (VAS). The subject will be instructed to complete entries from baseline assessment (prior to first dose) until 5 days after last dose of HD IL-2 for endpoint analysis. During inpatient admissions, subjects will complete diary entries before each dose (q8 hours). As an outpatient, subjects will complete diary entries on a daily basis. Recording of whether or not pruritus was observed will also be collected within the subject diary. If a patient reports pruritus, the severity of pruritus on the 1-100 scale visual analogue scale (VAS) will also be collected. The study team will record any episodes of vomiting and the use of rescue therapy and ensure completion of patient diary during inpatient portion. Assessments will be made via telephone contact to determine onset of any episodes of CINV during outpatient portion. Safety assessments including adverse events (AEs) monitoring will be performed and assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.