In order to improve our understanding of the control of adipose tissue development in man by adipogenic and antiadipogenic factors we studied the effect of transforming growth factor beta (TGF beta) on the differentiation of human adipocyte precursor cells cultured in a serum-free medium. Addition of TGF beta at concentrations ranging from 5 to 100 pmol/l for 24 h at the beginning of the differentiation process resulted in a dose-dependent reduced expression of glycero-3-phosphate dehydrogenase (GPDH) activity. Continuous exposure of cells to TGF beta completely blocked differentiation even at a concentration of 5 pmol/l. Under these conditions cells were not able to accumulate lipid droplets. This inhibitory effect of TGF beta was not mediated by stimulation of cell proliferation. Exposure of newly developed fat cells to TGF beta was also associated with a significant suppression of GPDH activity. A 10-day incubation of cells with TGF beta reduced GPDH activity by more than 80% compared to controls. Despite this suppressive effect cells retained the typical fat cell-like morphology. In conclusion, these data clearly suggest that TGF beta exerts an inhibitory action on human adipose tissue development and reduces the activity of a lipogenic key enzyme in newly formed fat cells.