The effects of ethinylestradiol (EE2)(I) [57-63-6] were investigated on body weight, weights of fat depots, triglyceridemia, and lipoprotein lipase (LPL) [9004-02-8] activity of fat cells isolated from the parametrial fat pads of female rats. The cellular uptake of fatty acids liberated during hydrolysis was also evaluated. EE2 (≥0.6 μg/rat) reduced body weight gain and weights of fat depots. Triglyceridemia increased at doses of EE2 up to 6 μg and showed a relative reduction at 60 μg. In parallel, LPL activity responded to the hormone according to a biphasic pattern: EE2 increased LPL activity in the dose range 0.6-6.0 μg, whereas a decrease occurred at higher doses. Fat cells incorporated, as acylglycerol, 56.5% of the amount of fatty acid liberated enzymically during incubation, and this percentage was essentially unchanged by EE2. EE2 at 60 μg/rat decreased triglyceridemia and LPL activity and, as a consequence, decreased fat depots. By contrast, EE2 at doses up to 6 μg created a paradoxical situation where concomitant increases in triglyceridemia and LPL activity, which should have favored fat deposition, coexisted with fat depletion. Estrogens at doses below toxicity increased the secretion of triglyceride-rich lipoproteins by liver. Whereas the increase in LPL activity observed in this study at low doses of EE2 may reflect the LPL responses to liver-borne hypertriglyceridemia, the mechanism for the concomitant fat depletion is unclear. These data emphasize the complex effects of estrogen hormones on lipid metabolism