Lp(a) level is relatively stable in each individual and is mainly under genetic control. Attempts made to lower Lp(a) with pharmacological means gave conflicting results. In order to further evaluate the effect of hypocholesterolemic drugs on Lp(a) level, 66 patients with primary hypercholesterolemia were selected. The vast majority of the patients had Lp(a) concentration at the low end of the range of distribution, 7 had undetectable Lp(a) levels and only 2 had Lp(a) higher than 30 mg/dl. No relationship was found between Lp(a) level and serum and lipoprotein lipids. In 12 patients serum cholesterol was well controlled by diet alone and the patients continued the diet for up to 8 months. The other patients were randomly subdivided into 3 groups of therapy. The first group received slow release bezafibrate 400 mg once a day, the second one pravastatin 20 mg once a day and the third one simvastatin 10-40 mg once a day. Drug therapy lasted for 8 months. At the end of the period, 22 of 29 patients treated with the 2 HMG-CoA reductase inhibitors had Lp(a) higher than baseline. The difference was statistically significant in both groups of patients. No significant change in Lp(a) was observed in diet and in bezafibrate group. Serum and LDL cholesterol significantly decreased in all the 3 drug groups. The increase in Lp(a) after the 2 HMG-CoA reductase was small enough to have negligible effects on cardiovascular risk, but raises the problem of the role of LDL receptor in the catabolism of Lp(a).