The effects of cyclosporin on plasma lipoproteins and lipoprotein lipase (LPL) activity were studied in rats treated with different doses of the drug for periods ranging between 7 and 30 days. The treatment with cyclosporin resulted in an increase in plasma triglycerides and non-HDL-cholesterol, and a dose and time-dependent decrease of LPL activity and HDL-cholesterol, mainly because of a fall in the HDL2-cholesterol subfraction. The decrease of LPL activity was positively correlated (p < 0.01) with plasma HDL-cholesterol and HDL2-cholesterol and negatively with plasma triglycerides and non-HDL-cholesterol (p < 0.01). Our results indicate that the decrease in plasma LPL activity may be responsible for the increase in plasma triglycerides and the decrease in plasma HDL-cholesterol found in rats under cyclosporin treatment.