Yohimbine, an alpha 2-receptor antagonist, was examined for its suitability in the treatment of obesity. Twenty female obese outpatients were subjected to a 3-week low-energy diet (1,000 kcal/day), after which they were randomly allocated according to a double-blind study protocol to two treatments: 10 subjects received 5 mg yohimbine per os 4 times a day and 10 received a placebo for 3 weeks, in addition to a low-energy diet of 1,000 kcal/day. Before inclusion in the study, as well as the end of each of the 3-week treatment periods, thermogenesis (resting and exercise energy expenditure) was assessed by indirect calorimetry; serum noradrenaline concentration was taken as an index of sympathetic system activity and serum glycerol level as an index of lipolysis. Yohimbine significantly increased the mean weight loss in patients on a low-energy diet: 3.55 +/- 0.24 kg (yohimbine) vs. 2.21 +/- 0.37 kg (placebo), P less than 0.005. With yohimbine, a steady level of effort-induced energy expenditure and sympathetic system activity was maintained. No significant effect of yohimbine on lipolysis was observed under the experimental conditions of this study. In another group of 15 obese inpatients (11 women and 4 men) the influence of 15 mg yohimbine per os vs. placebo on gastric emptying of a radiolabelled solid meal was examined in a double-blind manner with the use of a gamma camera. No significant effect of yohimbine on gastric emptying was revealed--the mean gastric transit time was 42.0 +/- 0.4 min after placebo and 41.8 +/- 0.5 min after yohimbine. The results obtained warrant further research on the applicability of alpha 2-receptor inhibitory drugs as a supplementary management in the treatment of obesity.