In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-14C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l-1. The subjects' ages were 64 +/- 2.7 and 66 +/- 1.1 (mean +/- SEM) years in the COPD and control groups, respectively. TOR was 0.73 +/- 0.06 and 0.52 +/- 0.02 mmol min-1 (P < 0.05) in the basal state, 0.33 +/- 0.04 and 0.30 +/- 0.02 at an insulin level of 50 mU l-1 and 0.32 +/- 0.08 and 0.24 +/- 0.02 at an insulin level of 100 mU l-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98 +/- 0.08 and 0.75 +/- 0.06 mmol l-1 (P < 0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.