Sudden death behind the wheel from natural disease in drivers of four-wheeled motorized vehicles. The heart was studied in 30 persons who died suddenly from natural causes in the driver's seat of an automobile, truck or bus. Twenty had cardiac arrest while driving and the other 10 while sitting in the driver's seat of a parked vehicle. Of the 20 drivers, 16 died from atherosclerotic coronary artery disease (CAD): 12 (75%) had minor collisions and 4 did not. Of the 16 with fatal CAD, an average of 2.3 +/- 0.8 of the 4 major coronary arteries were narrowed greater than 75% in cross-sectional area (CSA) by plaque; of 668 five-mm segments of the 4 major (right, left main, left anterior descending, left circumflex) coronary arteries in 13 of these 16 cases, 27 (4%) were narrowed 96 to 100% and 127 (19%) were narrowed 76 to 95% in CSA by plaque. The remaining 4 drivers died from noncoronary conditions: aortic rupture associated with the Marfan syndrome in 1; cardiac sarcoidosis in 1; thoracic aortic dissection in 1; and severe mitral regurgitation from infective endocarditis, which had healed in 1. The other 10 persons were found dead in the driver's seat of a parked vehicle and 8 of them had fatal CAD. Of the 8 CAD victims, an average of 2.5 +/- 1.2 of the 4 major coronary arteries was narrowed greater than 75% by plaque; of the 283 five-mm segments of coronary arteries in 7 of the 8 cases, 44 (16%) were narrowed 96 to 100% and 69 (24%) were narrowed 76 to 95% in CSA by plaque. 