Obese subjects have elevated adipose tissue lipoprotein lipase activity per fat cell when compared with lean control subjects. This enzyme, which is rate limiting for the uptake and storage of lipoprotein triglyceride in adipose tissue, has been shown to be further elevated in a group of previously obese subjects who had been weight stable at a reduced weight for 4-28 mo. In the present prospective study of eight obese subjects, adipose tissue lipoprotein lipase activity was demonstrated to increase after weight stabilization at a reduced weight (0.33 mU/10(6) cells). In three subjects who lost weight and subsequently regained their lost weight, the enzyme activity increased after weight loss and then returned toward the original basal level with weight gain. One subject who maintained his weight loss for 10 mo. continued to have an elevated level of enzyme activity. Because adipose tissue lipoprotein lipase activity does not "normalize" after weight loss, we hypothesize that this enzyme may play a counterregulatory role in resisting deviation from a "set point" for fat mass or fat cell size and thereby predispose to reattainment of the original obese state.