This study investigated the potential for dexfenfluramine to improve biochemical and clinical risk factors for cardiovascular disease, in obese dyslipidaemic individuals. Dexfenfluramine, the dextro isomer of fenfluramine, has been shown to aid weight reduction and lower blood lipids in normal subjects, and to improve glucose tolerance and insulin sensitivity in subjects with diabetes mellitus. Twenty-nine overweight (mean weight 83.3 +/- 11.3 kg), hyperlipidaemic (mean total cholesterol 7.3 +/- 1.2 mol/l) subjects participated in a 12-week randomized double-blind parallel study of dexfenfluramine versus placebo. After an eight-week dietary run-in phase, subjects were randomised to treatment with either dexfenfluramine or placebo for 12 weeks. During the run-in, energy intakes fell in both groups (5.5% for dexfenfluramine, 5% for placebo, no significant difference between groups). Dietary composition improved, fat as a percentage of energy decreased (14%, P < 0.001, for dexfenfluramine; 11.7%, P < 0.05, for placebo), and carbohydrate increased (8.5%, P < 0.05, for dexfenfluramine; 5.6%, not significant, for placebo). During the treatment period, energy intakes in the dexfenfluramine group were further reduced by 7.5%, whereas there was no change in the placebo group (P = 0.02 between dexfenfluramine and placebo groups); however, nutrient composition remained constant for both groups. Side-effects were formally reported by 40% of subjects during the initial four weeks' treatment with dexfenfluramine with three subjects withdrawing from the study. Side-effects were largely resolved by week 4. Both groups lost weight similarly during the run-in but there were no significant changes in any biochemical parameters.(ABSTRACT TRUNCATED AT 250 WORDS)