OBJECTIVE: To evaluate a possible influence of a hereditary trait for obesity on the regulation of adipocyte metabolism in vitro in subcutaneous fat cells in obese and non-obese subjects. DESIGN: A biopsy from abdominal subcutaneous fat was obtained from consecutive subjects with or without a family trait for obesity. A positive family history of obesity was considered present if one or more of the first degree relatives had a BMI of 27 kg/m2 or more. SUBJECTS: 67 non-obese and 60 obese subjects, age 19-60 y. A family trait for overweight was present in 42 of the lean subjects and in 50 of the obese subjects. MEASUREMENTS: Fat cells were isolated and incubated in vitro with isoprenaline (a non-selective beta-adrenoceptor agonist), forskolin (activates the adenylyl cyclase) and dibutyryl cyclic AMP (stimulates the protein kinase hormone-sensitive lipase complex). Glycerol release was measured and used as lipolytic index. RESULTS: Maximal lipolytic response per g triglycerides was about 50% lower in obese subjects both with and without a positive heredity and in non-obese subjects with a family trait for obesity as compared to non-obese subjects without such trait (P=0.0001). Fat cell volume was twice as high in obese as compared to lean subjects. Drug-induced maximal glycerol release per fat cell in the obese subjects, regardless of family history of obesity, reached a similar level, but did not exceed that of the lean group without heredity. CONCLUSIONS: Obesity is associated with catecholamine resistance with a relatively ineffective lipolysis in fat cells, and presence of a family history of obesity was not associated with a further suppression of lipolysis. In the lean subjects, heredity for obesity significantly influenced lipolysis to similar low levels as in the obese subjects.