High-density lipoprotein (HDL) in cholesteryl ester transfer protein (CETP) deficiency is deficient in reverse cholesterol transport although HDL-cholesterol levels markedly increase in such patients. This may be responsible for the abnormal metabolism of pre beta 1-HDL, the initial acceptor of cell-derived cholesterol. To answer this question, we determined HDL subfraction levels in 8 CETP deficiency and 21 normolipidemic subjects. We also measured the rate of decrease in pre beta 1-HDL level by LCAT activity during the incubation at 37 degrees C for 90 min. We found that HDL2b was 2.4 times higher in CETP deficiency than in control [52.2 +/- 14.3, vs. 21.5 +/- 9.8% of plasma apoA-I(%AI), p < 0.005] while HDL2a and HDL3 were significantly lower in the former than in the latter (HDL2a; 25.5 +/- 8.0 vs. 40.4 +/- 6.5% AI, p < 0.005) (HDL3; 10.0 +/- 6.8 vs. 28.3 +/- 5.9% AI, p < 0.005). There were no significant differences in pre beta 1-HDL level between 2 groups (4.9 +/- 3.0 vs. 4.5 +/- 2.3% AI, NS). However, the rate of decrease in pre beta 1-HDL was significantly less in CETP deficiency than in control (-33.2 +/- 22.9 vs. -73.7 +/- 12.2%, p < 0.005). In conclusion, the metabolism of pre beta 1-HDL is delayed in CETP deficiency. It is suggested that the esterification of cell-derived cholesterol removed by pre beta 1-HDL may be deficient in CETP deficiency.