The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m²) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery (PO_I); and after reaching stable body weight, at least 2 years after surgery (PO_II). A group of 7 control subjects (C), matched groupwise for sex, age and BMI with PO_II patients, was also studied. The M value at PO_I was significantly higher than at Ob (49.12 ± 8.57 vs 18.14 ± 8.57 μmol · kg⁻¹· min⁻¹). No statistical difference was observed between the PO_II and C groups. Similarly, glucose oxidation rate was significantly increased at PO_I with respect to Ob (24.2 ± 7.23 vs 9.42 ± 3.91 μmol · kg⁻¹· min⁻¹) and was not significantly different between PO_II and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to PO_I and from PO_I to PO_II (1517.1 ± 223.9 vs 1039.6 ± 283.4 vs 616.0 ± 77.6 μmol · l⁻¹). The same applied to basal plasma triglycerides (2.07 ± 0.77 vs 1.36 ± 0.49 vs 0.80 ± 0.19 g · l⁻¹). Weight decreased mainly in the late postoperative period (PO_I to PO_II 124.28 ± 11.22 to 69.71 ± 11.78, 83 % of total decrement), rather than in the early postoperative period (Ob to PO_I 135.25 ± 14.99 to 124.28 ± 11.22 kg, 17 % of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance. [Diabetologia (1997) 40: 599–605]