One hundred patients with primary hypercholesterolemia (total plasma cholesterol greater than or equal to 6.2 mmol/L [240 mg/dl]) were enrolled in an open, randomized, parallel comparative study of simvastatin and pravastatin. All patients started or continued a standard lipid-lowering diet for at least six weeks prior to entry into the four-week placebo baseline period. Fifty patients received simvastatin and 50 patients received pravastatin, both at the recommended starting dose of 10 mg/day, for a treatment period of six weeks. Total cholesterol levels were reduced by 24% (from 7.59 mmol/L to 5.80 mmol/L) with simvastatin, and by 15% (from 7.48 mmol/L to 6.35 mmol/L) with pravastatin. Low-density-lipoprotein cholesterol levels were reduced by 33% and 22% and high-density-lipoprotein cholesterol levels were increased by 10% and 7% with simvastatin and pravastatin, respectively. Plasma total triglyceride levels were reduced by 12% with simvastatin and by 6% with pravastatin. Adverse experiences were similar between treatment groups and both drugs were well tolerated. No patients were withdrawn from the study due to clinical adverse experiences; one patient in the pravastatin group required a reduction in dose to 5 mg/day due to insomnia. At the recommended starting dose, simvastatin had a significantly greater lipid-lowering effect than pravastatin. These results may have implications for the appropriate lipid-reduction therapy for patients at risk of coronary heart disease.