In the search for mechanisms supporting the weight-reducing effect of mazindol, we examined the influence of the drug on metabolism and gastric evacuation in two groups of 10 women each. In the first group the effect of mazindol on thermogenesis was assessed by indirect calorimetry, and blood glycerol concentration was taken as an index of lipolysis. After oral administration of 2 mg mazindol no significant changes were observed in the energy expenditure or lipolysis, either at rest or during exercise. In the second group, the influence of 2 mg mazindol, taken orally, on gastric emptying (GE) of a radiolabeled solid meal was examined with the use of a gamma camera. The drug significantly inhibited GE--the median GEt1/2 was 119 min after placebo vs. 230 min after mazindol. The mean +/- SE of the emptying index was 1.13 +/- 0.26 min-1 after placebo vs. 0.53 +/- 0.14 min-1 after mazindol. Mazindol elicited a delaying effect on the late phase of GE, as confirmed by a significant decrease of the shape parameter (S) of the power-exponential fitted GE curves, 2.09 +/- 0.22 after placebo vs. 1.61 +/- 0.24 after mazindol, and by the comparison of the amount of food emptied from the stomach: 30.7 +/- 6.1% after placebo vs. 17.8 +/- 4.0% after mazindol, at 80 min, and 38.9 +/- 6.2% after placebo vs. 20.6 +/- 4.3% after mazindol, at 90 min of the GE measurement.