The efficacy of once-daily versus twice-daily dosing of pravastatin was determined in men with primary hypercholesterolemia. The same group of patients was used in the two studies. In the once-daily study, 18 patients took 20 mg of pravastatin at bedtime for four weeks and then 40 mg of pravastatin for an additional four weeks. In the twice-daily study, 22 patients took 10 mg or 20 mg of pravastatin twice daily for four weeks. Total cholesterol was reduced 18% in the 20-mg once-daily group, 20% in the 10-mg twice-daily group, 23% in the 40-mg once-daily group, and 24% in the 20-mg twice-daily group; the respective reductions in low-density cholesterol were 27%, 28%, 32%, and 34%. All these reductions were statistically significant; no between-group differences were significant. Pravastatin was well tolerated and no patients dropped out because of side effects.