A causal link between hypercholesterolemia due to elevated plasma concentrations of LDL and VLDL remnants of CAPD patients has been established. The effects of 24 weeks of treatment with Simvastatin, a new HMG coenzyme A-reductase inhibitor (at 20 and 40 mg/day) on serum lipid, lipoprotein, and apolipoprotein A-I and B concentrations, as well as safety parameters and subjective side effects, were evaluated in eight patients (mean duration CAPD 24.80 +/- 7.50 months, age 54.50 +/- 13.70 years). Maximal effects on plasma lipoprotein and apolipoprotein concentrations were achieved after 4 weeks, and remained stable thereafter during the study. Mean fasting plasma cholesterol concentrations decreased from 280.5 +/- 60.2 mg% to 190.2 +/- 40.4 mg/dl (p less than 0.005) (-47%); mean plasma LDL-cholesterol concentrations also decreased from 257.6 +/- 13.4 mg% to 190.5 +/- 15.4 mg/dl (p less than 0.001) (-35%). Apolipoprotein A and B concentrations decreased significantly from 1.78 +/- 0.19 to 1.40 +/- 0.22 g/L (p less than .005) and 1.81 +/- 0.26 to 1.38 +/- 0.20 g/L (p less than .005). These data substantiate the view that Simvastatin is well tolerated and that no serious clinical or adverse laboratory effects have been observed. It appears to be a promising drug for the effective control of hyperlipemia in a large proportion of hypercholesterolemic patients, reducing their cardiovascular morbidity while on CAPD.