High density lipoprotein subfractions with a pre-beta migration play a key role in the reverse cholesterol transport. The origin of these particles is not yet clearly defined. We propose to verify a possible origin of these particles during the catabolism of high density lipoprotein2 (HDL2) by hepatic lipase using two different models. A rat liver perfusion of native human HDL2 in the presence of heparin induced, after 30 min, the formation of the pre-beta 1 HDL subspecies. Human HDL2 enriched with triacylglycerols, perfused in the same conditions, led after 15 min to an enhanced production of this pre-beta 1 HDL population, as compared with the results obtained with native HDL2. A reduction of the alpha-HDL2 fraction was also evident. After perfusion, a similar formation of pre-beta 1 HDL from triacylglycerol-rich HDL2 was observed in absence of heparin. When these HDL2 were incubated in vitro for 120 min at 37 degrees C in the presence of partially purified rat hepatic lipase, the appearance of pre-beta 1 HDL was again found and associated with a decrease in size of the remaining alpha-HDL subfractions as compared with original HDL2. On the contrary, the incubation of the same HDL2 with snake venom phospholipase A2 produced no pre-beta HDL. These results evidence the role of the triacylglycerol lipase activity of hepatic lipase in the formation of pre-beta 1 HDL from triacylglycerol-rich HDL2.