The effect of DMSO on cholesterol and bile acid metabolism was studied in rats. Male Sprague-Dawley rats were randomly assigned to one of two groups and given either tap water or 2% DMSO (v/v) in tap water to drink for 9 days. Both food (stock rat diet) and water were available ad libitum. Animals in both groups gained weight equally throughout the study. They also had similar liver weights (g/100 g body wt) at the end of the study (control: 5.0 +/- 0.1 (N = 6) vs DMSO: 4.9 +/- 0.1 (N = 6]. The activity of hepatic cholesterol 7 alpha-hydroxylase (pmole/mg/min), the rate-limiting enzyme of bile acid biosynthesis, was significantly (P less than 0.005) reduced in the treated animals (control: 9.7 +/- 1.0 (N = 6) vs DMSO: 4.3 +/- 0.7 (N = 6)). Plasma cholesterol (mg/dl) was significantly (P less than 0.005) elevated in the treated animals (control: 90 +/- 3 (N = 6) vs DMSO: 107 +/- 4 (N = 6)), a finding consistent with the reduced CH-7 alpha hydroxylase activity in this group. DMSO treatment did not affect either microsomal cholesterol content or hepatic glutathione content. Thus, this study has shown that DMSO treatment per se can affect cholesterol and bile acid metabolism. However, the precise mechanisms whereby DMSO exerts the observed effects are not known.