Age has been shown to influence drug metabolism but effects of aging could be due to other variables that influence metabolism and differ with age. Plasma half-life and metabolic clearance rate of antipyrine were studied in 307 healthy male subjects, aged 18 to 92. Half-life was 16.5 % longer and metabolic clearance rate was 18.5% less in a group of the older than in the younger subjects. Alcohol consumption, caffeine consumption, and cigarette smoking all were lower in the older subjects. Both caffeine and cigarette use were positively correlated with the rate of antipyrine metabolism. Multiple regression analysis showed that the effect of smoking was partially responsible for the age differences in antipyrine metabolism. Smoking explained 12% of the variance in metabolic clearance rate and age explained 3%. Our results suggest that studies attempting to quantify the effects of aging on drug metabolism must also take into account other factors that differ with age.