To examine the interrelationships of cigarette smoking, relative weight, and the occurrence of natural menopause, the authors prospectively evaluated the experience of 66,663 female US registered nurses who were premenopausal in 1976. Over a two-year period, 5004 women became post-menopausal. Current smokers were more likely than past or never smokers to develop menopause, although the effects of smoking diminished with age. The rate ratios of menopause for current smokers vs. never smokers (with 95% confidence limits) for women aged 30-39, 40-44, 45-49, and 50-55 years were 1.90 (1.10-3.28), 2.16 (1.73-2.69), 1.53 (1.41-1.67), and 1.20 (1.12-1.28). These rate ratios were not appreciably affected by adjustment for relative weight. Median ages at menopause were 52.4 for never smokers and 51.9, 51.0, 50.7, and 50.4 years for women who currently smoked 1-14, 15-24, 25-34, and 35 or more cigarettes per day. A crude linear relationship between relative weight and occurrence of menopause was observed. Comparing the leanest and heaviest quintiles, rate ratios for menopause among women aged 30-39, 40-44, 45-49, and 50-55 years were 1.42 (0.74-2.75), 1.26 (0.95-1.69), 1.25 (1.13-1.41) and 1.08 (0.99-1.19). The effect of relative weight was in part explained by the tendency of current smokers to weigh less than nonsmokers. After adjustment for current cigarette consumption a weak linear relationship between relative weight and menopause remained among women who smoked, although no such association was seen among nonsmokers.