Hypercholesterolemia may pose a substantial risk for cardiovascular disease. The present investigation was designed to evaluate the safety and efficacy of the cholesterol synthesis inhibitor, lovastatin, in 13 nephrotic patients with 5.6 +/- 0.7 g/24 h of albuminuria. All patients were maintained on a low cholesterol diet throughout the study. After a 4-week placebo period, lovastatin was administered, 20 mg twice daily for 6 weeks. Lovastatin reduced total cholesterol by 27% from 8.6 +/- 0.6 mmol/L (331 +/- 24 mg/dL) to 6.3 +/- 0.4 mmol/L (242 +/- 17 mg/dL) (P less than 0.01), low-density lipoprotein cholesterol by 27%, from 5.8 +/- 0.5 mmol/L (223 +/- 20 mg/dL) to 4.2 +/- 0.6 mmol/L (163 +/- 22 mg/dL) (P less than 0.01), and apolipoprotein B by 29%, from 153 +/- 12 mg/dL to 109 +/- 8 mg/dL to 109 +/- 8 mg/dL P less than 0.01). Triglycerides and very-low-density lipoprotein (VLDL) cholesterol levels were also reduced by 30% and 37%, respectively (P less than 0.01). High-density lipoprotein (HDL) cholesterol, and apolipoproteins A-1 and A-2 were not significantly altered. Renal function and urine protein excretion were not affected by lovastatin. Although one patient developed diarrhea and discontinued treatment before completing 6 weeks of lovastatin, the other 12 patients had no adverse effects. In this short-term study, lovastatin therapy had few side effects and had favorable effects on the lipoprotein profile of nephrotic syndrome patients.