Platelet function parameters were studied in type II hyperlipoproteinemics in relation to baseline and drug-induced changes in serum cholesterol levels. There were no significant differences between 28 type II hyperlipoproteinemics and 19 normal subjects in baseline values for platelet aggregation, thromboxane generation, sensitivity to prostacyclin, plasma platelet factor 4 or beta-thromboglobulin. Eleven of the hyperlipoproteinemic patients were treated with a combination of the cholesterol-lowering drugs probucol and colestipol. The drug treatment resulted in statistically significant lowering of serum total and low-density lipoprotein (LDL)-cholesterol levels (30% reduction of mean LDL-cholesterol, p less than 0.01); however, there was no significant change in any of the platelet function parameters after the drug treatment compared with placebo. These results provide evidence against a relationship between serum cholesterol levels and in vitro platelet function.