The response of plasma growth hormone and cortisol to the intramuscular injection of 1 mg glucagon was used to assess anterior pituitary function in a group of 97 normal subjects (23 men, 74 women). Ninety-three subjects (96%) responded with a peak GH of at least 8 ng/mL, and 89 (92%) had either a peak cortisol of at least 500 nmol/L (18 micrograms/dL) or a maximal increment in plasma cortisol of at least 250 nmol/L (9 micrograms/dL) above the baseline. In 12 subjects, a second test showed that the responses were reproducible. A greater proportion of subjects over the age of 50 failed to achieve a peak GH of 10 ng/mL (7 of 20, 35%) compared to those who were either under 30 (1 of 37, 2.7%) or between 30 and 50 (4 of 40, 10%) (chi 2 = 12.85, P less than .005). GH responses were not affected by sex or elevation of the basal level of GH. In contrast, cortisol responses were smaller in men and in individuals with high basal cortisol levels but were not affected by age. Mild nausea in approximately 30% of subjects (29 of 97), and transient vomiting and retching in approximately 10% (10 of 97) were the only side effects that were noted. Glucagon is therefore a safe and reliable alternative to insulin-induced hypoglycemia for the assessment of both somatotrophic and corticotrophic function.