The Multiple Risk Factor Intervention Trial (MRFIT), conducted in 1973-1982, provided a unique opportunity to study the effect of passive smoking on men whose wives smoke. MRFIT participants who reported at entry that they had never smoked tobacco products were classified according to the smoking status of their wives. Men with wives who smoked had similar mean levels of serum thiocyanate (54.3 vs. 53.9 mumol/liter, p = 0.83) but higher mean levels of expired carbon monoxide (7.7 vs. 7.1 ppm, p = 0.001). Lower levels of pulmonary function (by maximum forced expiratory volume in one second) were also observed in these men (3,493.1 vs. 3,591.9 ml, p = 0.04). The relative risks, for men whose wives smoked compared with men whose wives did not smoke, for the endpoints coronary heart disease death, fatal or nonfatal coronary heart disease event, and death from any cause were 2.11 (p = 0.19, 95% confidence interval (CI) 0.69-6.46), 1.48 (p = 0.13, 95% CI 0.89-2.47), and 1.96 (p = 0.08, 95% CI 0.93-4.11), respectively. When smokers who quit prior to entry were included in the analyses, the relative risks, for men whose wives smoked compared with men whose wives did not smoke, for the above endpoints were 1.45 (p = 0.25, 95% CI 0.77-2.73), 1.19 (p = 0.29, 95% CI 0.85-1.65), and 1.72 (p = 0.01, 95% CI 1.12-2.64), respectively. These relative risk estimates did not change appreciably after adjusting for other baseline risk factors. The results suggest that passive exposure to cigarette smoke may have a deleterious impact on the health of nonsmokers and that nonsmokers may be at an increased risk of death through passive exposure to cigarette smoke.