The effects of β-endorphin (β-Ep) on plasma glucose levels in rats and on glucose metabolism in isolated rat liver cells were examined. Intravenous injection of β-Ep (5 μg/100 g BW) into ether-anaesthetized rats resulted in prompt and sustained hyperglycaemia with increases in the plasma glucagon and somatostatin levels and decrease in the plasma insulin level. When liver cells isolated from fed rats were incubated in the presence of β-Ep at concentrations of 6 × 10-8 M to 6 × 10-7 M, glucose release into the medium increased within 15 min in a dose-related manner. Time course experiments showed that (β-Ep increased the level of cyclic AMP within 3 min. Significant increase in gluconeogenesis in liver cells isolated from fasted rats was also observed on addition of 10-7 M β-Ep in the presence of 10 mM L-lactate. These results suggest that the hyperglycaemia induced by β-Ep may be caused, at least in part, by the effects of β-Ep on releases of pancreatic hormones and glucose production in liver cells.