OBJECTIVE To study the associations of obesity (as body mass index (BMI)), of body fat distribution (as waist to hip ratio (WHR)) and of beta-endorphinaemia (beta-EP-aemia) with fasting insulin and glucose concentrations, with insulin secretion (as first phase insulin response (FPIR)) and with insulin sensitivity (SI) in obese women. METHODS a cross-sectional study of insulin sensitivity in obese women. METHODS 45 obese women (age: 20-70 y, BMI: 27-50). METHODS Frequently sampled intravenous glucose tolerance test (FSIGTT), FPIR, fasting glucose, fasting insulin, BMI, body fat topography (WHR), beta-EP-aemia, plasma ACTH. RESULTS In univariate analysis the following positive associations were observed: fasting glucose with age and WHR, fasting insulin with BMI and WHR, beta-EP plasma concentration with WHR; SI was negatively associated with BMI, WHR and beta-EP plasma concentrations. This pattern of associations remained unaltered in multivariate analysis including age, BMI and WHR as independent variables. The contribution of beta-EP plasma concentrations to SI variability was corroborated by a stepwise multiple regression analysis: 53.8% of SI variation could be explained by BMI (30.7%), by beta-EP plasma concentrations (17.2%) and by WHR (5.9%). Finally, women were divided into two groups according to whether they had a peripheral (P-BFD, WHR < or = 0.80, n = 24) or an abdominal (A-BFD, WHR > or = 0.85, n = 16) body fat distribution. After adjustment for age and BMI, SI values were lower while beta-EP and ACTH plasma concentrations were higher in the A-BFD compared to the P-BFD group. In this latter group, 54.8% of SI variation was explained by the same variables as in the whole group. In the A-BFD group, higher WHR was associated with lower FPIR. CONCLUSIONS 1) The major finding of this study is that, in non-diabetic obese women (especially those with a P-BFD), higher beta-EP plasma concentrations are associated with lower insulin sensitivity. This association is independent of both the magnitude of obesity and the pattern of fat distribution, although these two parameters are strong predictors of SI. 2) The major reduction in SI observed in women with A-BFD probably results from the additive effects of obesity, of elevated beta-EP plasma concentrations and of metabolic and endocrine alterations in relation with the central pattern of fat distribution.