BACKGROUND Acipimox is a hypolipidaemic agent reducing serum concentrations of triglycerides and non-esterified fatty acids. Acipimox may reduce triglyceride synthesis by decreasing non-esterified fatty acid availability from adipocytes, but this effect has yet to be demonstrated in vivo. Lipolysis after acipimox treatment was examined in subcutaneous adipose tissue of severely obese subjects with associated metabolic disorders. METHODS The microdialysis technique was performed in abdominal subcutaneous adipose tissue of eight hyperinsulinaemic subjects. After oral treatment with acipimox, glycerol concentration was determined as an index of lipolysis rate. Blood flow was assessed by the ethanol escape technique. The rates of release of glycerol from human adipose tissue maximally stimulated by norepinephrine were also investigated in the presence of acipimox. Eight weight- and age-matched subjects served as a control group. RESULTS Under acipimox treatment, basal glycerol release decreased in subcutaneous adipose tissue, whereas no effect was observed on blood flow. In stimulated adipose tissue acipimox showed no effect. CONCLUSIONS In the present study basal glycerol outflow from adipose tissue was inhibited by acipimox. The anti-lipolytic action of the agent may diminish elevated plasma concentrations of free fatty acids in subjects with severe obesity.