OBJECTIVE Prolactin has important biological actions in several species which include metabolic control and water/electrolyte balance. However, human PRL has generally been characterized as a mammotrophic hormone and it is unknown whether PRL has any important metabolic actions. This study was thus conducted to evaluate the effect of hyperprolactinaemia on peripheral muscle glucose metabolism. DESIGN The study was designed to determine forearm muscle glucose uptake and utilization (oxidative and nonoxidative metabolism) in normal and hyperprolactinaemic subjects in the post-absorptive state and for 3 hours after the ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrates combined with local indirect calorimetry. PATIENTS Eight hyperprolactinaemic patients (HP group, 6 females and 2 males) and ten normal subjects (N group, 7 females and 3 males) were studied. The hyperprolactinaemic patients showed no clinical or laboratory evidence of acromegaly or hypothyroidism and were not using any PRL releasing drugs. MEASUREMENTS Forearm blood flow was measured by capacitance plethysmography and arterial and venous blood samples were drawn simultaneously to determine plasma glucose, serum FFA, total blood CO2 and O-2 and serum insulin in the post-absorptive state (0 time) and at 30, 60, 120 and 180 minutes after glucose ingestion. RESULTS No significant difference in glucose uptake by the forearm muscle tissue was observed between the N and HP groups (823 +/- 103 vs 828 +/- 110 mu mol/100 ml forearm 3 h, respectively), nor were any significant differences observed in the intracellular utilization of glucose (oxidative and non-oxidative metabolism). However, the serum insulin levels after glucose ingestion were significantly higher in hyperprolactinaemic patients than in normal subjects, especially at 30 (N 283 +/- 46 vs HP 581 +/- 133 pmol/l) and 60 minutes (N 291 +/- 37 vs HP 544 +/- 61 pmol/l). Furthermore, after glucose ingestion the suppression of serum FFA levels was smaller in the hyperprolactinaemic patients than in normal subjects. CONCLUSIONS This study demonstrated that insulin resistance is associated with the presence of spontaneous human hyperprolactinaemia. The hyperinsulinaemia detected in the hyperprolactinaemic patients after the oral glucose stimulus did not determine a proportional increase in forearm glucose uptake and utilization, which were similar to the normal levels. The suppression of serum free fatty acid concentrations was also smaller in hyperprolactinaemic patients during the oral glucose challenge, suggesting an impaired antilipolytic effect of insulin.