We have compared the effects of two dietary regimens with different macronutrient compositions--a macrobiotic diet and a Western diet--on drug metabolism and plasma lipids in seven healthy volunteers. The macrobiotic diet, high in carbohydrate, low in protein and fat, and devoid of animal food sources, was eaten for a ten day control period, as was the Western diet, high in calories, fat, and protein, as well as animal food sources. We determined the influences of these diets on the clearance of orally administered antipyrine, oxazepam, and methadone, as well as on plasma lipids. There was a statistically significant change in antipyrine clearance as well as in plasma LDL-cholesterol and HDL-cholesterol after the dietary periods. This suggests that the influence of dietary changes may have some effect on the clearance of therapeutic drugs. However, this is not universal and is probably important when the drug is highly dependent on the mixed-function oxidase system.