Thirty-three consecutive unselected patients with primary hypercholesterolemia received niceritrol 1.5 g daily for 12 weeks, with the effect of administering divided dose (twice daily (b.i.d.) and three times daily (t.i.d.)) evaluated. The serum concentrations of lipoprotein(a) (Lp(a)), lipids, the major apolipoproteins (apo), cholesteryl ester transfer activity and fibrinogen were determined before and after treatment. The b.i.d. and t.i.d. regimens each significantly reduced the serum levels of total cholesterol and triglyceride. The mean changes in serum lipids and lipoproteins did not differ significantly between the two groups. After 12 weeks of treatment, there was a significant decrease in total plasma cholesterol, triglyceride, low density lipoprotein cholesterol, apo A-II, apo B and fibrinogen and an increase in the high density lipoprotein cholesterol levels. Although the serum level of Lp(a) did not change in every patient, niceritrol significantly reduced the serum Lp(a) level in those with an initially high level of Lp(a) (greater than or equal to 20 mg/dl).