High-density lipoprotein (HDL) metabolism has been reviewed from information derived from turnover studies in humans. The two major HDL apoproteins AI and AII have different removal rates, reflecting the faster catabolism of HDL2 than of HDL3. This is caused by the continual cycle of formation of HDL2 from HDL3 and its reversion to HDL3, in response to the need to transport cholesterol and other lipids from extrahepatic cells and catabolized triglyceride-rich lipoproteins. The conversion of HDL2 to HDL3 is mediated through a hepatic lipase. Because this lipase is inhibited by estrogen and stimulated by androgens, women have higher HDL2 levels than men. The synthesis of apoproteins AI and AII is also higher in women than in men. Nutrition also influences HDL turnover. Carbohydrates increase AI and HDL2 removal, whereas polyunsaturated fatty acids inhibit synthesis. Vegetarians show high HDL removal rates. Thus low-fat, low-cholesterol diets generally lead to lower HDL levels. Disorders that alter HDL composition (such as alcoholic liver disease or Tangier disease) accelerate HDL removal. Other HDL proteins such as apoproteins C and E show faster turnover rates than AI and AII, since the former exchange with triglyceride-rich lipoproteins and participate in their catabolism. Diminished exchange of apoprotein C from HDL to chylomicrons may be responsible for the diminished catabolism of these particles in type V hyperlipoproteinemia. The unusual turnover characteristics of HDL apoprotein AIV are reviewed, suggesting a dual role for this protein in both triglyceride and cholesterol transport. The striking relationship between very low-density lipoprotein (VLDL) and HDL metabolism is expressed in an inverse association between their respective removal rates.(ABSTRACT TRUNCATED AT 250 WORDS)