The aim of this study was to delineate the mechanisms by which varying periods of starvation decrease lipoprotein lipase (LPL) activity in rat adipose tissue. LPL mRNA levels and rates of LPL synthesis, degradation and secretion were compared in adipocytes from male rats that had been fed or starved for 1 or 3 d. The decreased LPL activity after 3 d of starvation (-76%) was explained mainly by a 50% decrease in the relative abundance of LPL mRNA levels (P < 0.05) and a parallel 50% decrease in relative rates of LPL biosynthesis (P < 0.05). In contrast, starvation for 1 d decreased total LPL activity by 47% (P < 0.05) but did not affect LPL mRNA levels or relative rates of LPL biosynthesis. Pulse-chase studies demonstrated that 1 d of starvation increased the rate of degradation of newly synthesized LPL (P < 0.05) and markedly decreased its secretion into the medium (P < 0.05). A decrease in overall protein synthesis also contributed to the decreased LPL activity after 1 and 3 d of starvation. We conclude that the relative importance of pre- and post-translational mechanisms in regulating adipose tissue LPL activity depends on the duration of starvation. During short-term starvation, degradation of newly synthesized LPL is an important determinant to its secretion from the adipocyte and hence its functional activity at the capillary endothelium.