OBJECTIVE To investigate the effect of dexfenfluramine (d-F) on basal and isoproterenol stimulated lipolysis in human fat cells in vitro. METHODS Adipocytes were incubated in Krebs-Ringer-Hepes buffer either with 10(-6) M or 10(-7) M isoproterenol alone, with 0.02-200 micrograms/ml (74.7 nmol/l-747 mumol/l) of d-F or both. METHODS Glycerol release at 2 h incubation time was measured as an estimate for lipolysis. RESULTS The addition of d-F did not significantly influence basal lipolysis of 58.6 nmol/2 h. Stimulation by 10(-6) M and 10(-7) M isoproterenol increased glycerol release to 92.5 nmol/2 h and 83.4 nmol/2 h, respectively. Adding increasing doses of d-F and 10(-6) M isoproterenol caused a dose-dependent inhibition of isoproterenol stimulated lipolysis. Glycerol release was significantly decreased to 84.1 nmol/2 h at 20 micrograms/ml, to 77.8 nmol/2 h at 60 micrograms/ml and to 61.9 nmol/2 h at 200 micrograms/dl d-F. Glycerol release induced by 10(-7) M isoproterenol was significantly inhibited to 69.7 nmol/2 h at 20 micrograms/ml, to 61.5 nmol/2 h at 60 micrograms/ml and to 51.9 nmol/2 h at 200 micrograms/ml d-F. 50% inhibition occurred at 80 micrograms/ml d-F with 10(-6) M isoproterenol and at 28 micrograms/ml with 10(-7) M isoproterenol. CONCLUSIONS d-F may decrease the release of free fatty acids from adipose tissue. This would lead to a reduced flux to the liver and may partly account for the triglyceride lowering effect of d-F in obese subjects.