To assess the effects of acute dietary saturated fat intake on glucose-induced insulin secretion rate (ISR), measured by the C-peptide deconvolution method, and on insulin clearance and sensitivity, five obese and five normal-weight women (controls) were studied after either a 100g oral butter load or a 100ml water load. At 120min after the oral load a hyperglycaemic clamp was performed over 180min. A dramatic increase of ISR occurred after butter compared with the water challenge in the controls (1305·6 (SE 124·1) v. 616·1 (SE 52·5) pmol/min; P<0·01) and to a lesser degree in the obese subjects (1975·0 (SE 44·1) v. 1417·5 (SE 56·0) pmol/min; P<0·05). Insulin sensitivity was impaired after butter (0·60×10−2 (SE 0·11×10−2) v. 2·26×10−2 (SE 0·32×10−2) ml/min per kgFFM per (pmol/l); P<0·01) in the controls but not in the obese group. Insulin clearance during the clamp was reduced after butter compared with after the water load only in the controls (0·89 (SE 0·22) v. 1·70 (SE 0·15) litres/min; P<0·01). The data are consistent with the hypothesis that acute excess lipid availability may lead to a compensatory elevation in glucose-induced insulin secretion as a result of the decline in insulin sensitivity and a reduced insulin clearance.