Hepatic lipase is emerging as a major factor in the control of HDL metabolism. Hepatic lipase plays a central role in the hydrolysis of HDL2 triglycerides and phospholipids and in the concomitant apolipoprotein A-I efflux from this density class. New data suggest that allelic variation at the hepatic lipase gene locus accounts for 25% of the total variability in HDL cholesterol. Recent information suggests that this lipase may enhance the uptake of lipoproteins by cell surface receptors.