Several drugs were tested for their ability to inhibit lipogenesis in human adipose tissue. Only fenfluramine was found to inhibit the incorporation of T-palmitate and 14C-glucose into neutral lipid in intact tissue. This effect was observed at drug concentrations above 1 mM. Fenfluramine inhibited lipogenesis in broken-cell preparations of human adipose tissue at concentrations of 1 mM and above. However, in this system the N-benzoyloxyethyl derivative of fenfluramine, S. 1513, was also found to inhibit lipogenesis. This drug was more potent than fenfluramine, a significant inhibition being observed at 0.4 mM During inhibition of lipogenesis in homogenates of adipose tissue by fenfluramine radioactitivity was found to accumulate in long-chain acyl-CoA which suggests that the drug may interfere with acylation of glycerol 3-phosphate. Evidence that fenfluramine may have a similar effect in vivo was considered, but the results were not statistically significant.