Both "big" platelets and hyperlipidemia are associated with increased coronary risk. This study was undertaken to search for a possible effect of various hypolipidemic drugs on big platelets. The percentage of big platelets, assessed microscopically, was measured in 66 patients who had hyperlipidemia of various types. Twenty-seven patients with hypertriglyceridemia were randomly selected to receive either fish oil or placebo in a crossover study. Another group of 39 patients with hypercholesterolemia, among them 13 with heterozygous familial hypercholesterolemia (FH), received lovastatin. The pretreatment level of big platelets was elevated, and similar in all groups: 23.3 +/- 12% versus 22 +/- 9%, in the fish oil versus placebo group, 19.1 +/- 6.3% versus 24 +/- 11% in the FH versus non-FH primary hypercholesterolemia group (reference value, 6.8 +/- 3.5%). After treatment, despite the improvement in lipoprotein profile, the percentage of big platelets did not change. The relationship between lipid reduction and big platelets is thus questionable, and necessitates further study.