To investigate the role played by glucagon in the regulation of plasma potassium, we have examined the behaviour of this ion during four 2 h infusions of saline, glucagon (200 ng/min), cyclic somatostatin (priming dose of 50 microgram followed by 5.8 microgram/min) and somatostatin plus glucagon in 6 normal volunteers. Glucagon alone produced no change in potassium, despite an increase in insulin. Somatostatin, in addition to depressing insulin, produced a slight but significant (P < 0.01) increase in potassium (delta max: 0.2-0.8 mmol/1: mean +/- SEM, 0.4 +/- 0.1). Infusion of somatostatin together with glucagon suppressed the glucagon-induced increase in insulin and greatly augmented the increase in blood glucose. Potassium rose significantly more (P < 0.02) than after somatostatin alone (delta max: 0.5-1.3 mmol/l; mean 0.9 +/- 0.1), indicating that hyperkalaemia results from hyperglucagonaemia in the absence of insulin. Evidence is presented that this last phenomenon is not mediated by hyperglycaemia or by a reduction in aldosterone secretion. It is suggested that low blood insulin and increased glucagon could be one of the mechanisms that underlie or magnify the hyperkalaemia observed in cases of serious stress or decompensated diabetes.