The serum decay of rat serum high-density lipoprotein (HD lipoprotein), labelled biosynthetically with (32)P in the phospholipid or with (3)H in the cholesteryl ester moiety, was measured in rats after partial hepatectomy or sham operation. The serum decay of (3)H-labelled HD lipoprotein cholesteryl esters was biexponential. In sham-operated rats the t((1/2)) values for the rapid phase and the slow phase were 0.2+/-0.1h and 4.2+/-0.4h (means+/-s.e.m.) respectively. After removal of two-thirds of the liver the t((1/2)) value of the rapid phase did not change (0.1+/-0.1h), whereas the t((1/2)) value of the slow phase increased to 5.7+/-0.8h. Partial hepatectomy hardly changed extrahepatic tissue radioactivities, whereas the percentage of the injected dose recovered in the liver 6h after injection decreased from 34.0+/-1.9% before to 13.5+/-1.6% after partial hepatectomy. The (32)P-labelled HD lipoprotein phospholipids showed a rapid monoexponential decay from serum with t((1/2)) values of 0.71+/-0.3h and 1.48+/-0.11h after sham operation or partial hepatectomy respectively. The tissue (32)P radioactivities in the shamoperated rats, measured 1h after injection, were 46.0+/-1.7% (liver), 1.7+/-0.3% (adipose tissue), 3.7+/-1.2% (skeletal muscle) and 3.0+/-0.0% (erythrocytes) of the injected dose. Only the value for liver was affected by partial hepatectomy and decreased to 16.7+/-3.8%. In a previous publication [Van Tol, Van Gent, Van't Hooft & Vlaspolder (1978) Atherosclerosis29, 439-448] we showed in a highly comparable experimental setting that the turnover rates of HD apolipoproteins A and C in vivo are not influenced by removal of two-thirds of the liver. From the present study it is clear that the removal rates of radioactive HD lipoprotein cholesteryl esters and HD lipoprotein phospholipids from serum in vivo are decreased by partial hepatectomy. The results indicate the possibility of partly separate metabolic pathways of HD apolipoproteins A and C, HD lipoprotein cholesteryl esters and HD lipoprotein phospholipids. The phospholipids and cholesteryl esters of HD lipoprotein are metabolized predominantly by the liver. Possible mechanisms for the hepatic uptake and metabolism of HD lipoprotein cholesteryl (esters) and phospholipids are discussed.