The metabolic effects of acute (4 h) and prolonged (24 h) growth hormone excess at pathophysiological concentrations were studied by growth hormone administration to normal subjects with and without somatostatin induced insulin deficiency. Acute growth hormone excess produced mild hyperinsulinaemia, but blood glucose concentrations were unaltered whereas chronic growth hormone excess caused a small (0.5 mmol/l) but significant rise in overnight-fasting blood glucose concentration together with a similar rise in fasting insulin levels (Mean +/- SEM 9 +/- 1 v 4 +/- 1 mU/l, p less than 0.01). When insulin secretion was suppressed by somatostatin, a hyperglycaemic effect of acute growth hormone excess was unmasked, and the hyperglycaemic effect of chronic growth hormone excess was exaggerated. Acute growth hormone administration without somatostatin had a mild ketogenic action despite stimulated insulin secretion but no change in plasma non-esterified fatty acid or blood glycerol levels was observed. Somatostatin magnified the ketogenic effect of acute growth hormone excess, and unmasked a lipolytic action. Prolonged growth hormone excess had a lipolytic action that was increased by somatostatin, although the ketogenic effect of growth hormone was only seen during somatostatin induced insulin deficiency. The acute hyperglycaemic, lipolytic and ketogenic actions of growth hormone in normal subjects are limited by a compensatory rise in insulin secretion although with chronic exposure hyperglycaemic and lipolytic effects are seen. In insulin-deficient states, however, elevated growth hormone levels could be important in promoting hyperglycaemia and hyperketonaemia.