Lipoprotein lipase was measured in gluteal adipose tissue from nine obese (90.6±2.7 kg) women fasting and after the intravenous infusion of insulin and glucose before, immediately after, and 3 mo subsequent to a 14.0±1.8% (i±SEM) weight reduction. Fasting adipose tissue lipoprotein lipase activity (ATLPL) decreased from 5.3 to 2.3 nEq FFA/106 cells per mi (P < 0.02) immediately after weight reduction, yet after weight maintenance, higher levels were again found (6.1 nEq FFA/106 cells per min). Although responsiveness of ATLPL to 40 mU/m2 per min of insulin infusion over 6 h was absent before weight loss, increases were seen immediately after weight loss (AO.8, P = 0.05) and more so (A7.7, P < 0.01) after 3 mo. Moreover, whereas before weight loss the ATLPL response to ingested mixed meals (A 0.9) was minimal, in the maintained reduced-obese state a marked increase was seen (A12.6, P = 0.02). Thus, because ATLPL is important to lipid filling in adipose tissue, the maintenance of high levels of fasting ATLPL and the increase in enzyme responsiveness in the reduced-obese state could play an important role in the resumption of the obese state, which so commonly follows weight reduction.