We investigated the modulating effect of serum total triglycerides on the lipid composition of various lipoproteins, and on the response to gemfibrozil treatment. This placebo controlled study was conducted blind in 60 participants of the Helsinki Heart Study. An inverse relationship was observed between cholesterol content in all lipoprotein fractions and serum total triglyceride level. Gemfibrozil, in addition to changing the absolute amounts of lipoprotein lipids, also normalized the qualitative abnormalities associated with hypertriglyceridemia. Gemfibrozil increased the level of HDL-cholesterol with the main effect on HDL 3-subfraction. The observed reduction in LDL-cholesterol was dependent on the initial triglyceride level.