Fourteen children and adolescents with slight constitutional growth retardation (12 males and two females) aged from 7 1/2 to 18 1/2 yr underwent an oral glucose tolerance test (OGTT 1.75 g/Kg followed at 180 min by an i.v. glucagon injection (0.03 mg/Kg). On a separate occasion these children underwent a simple i.v. glucagon test. Comparing the glucose and insulin response in the two glucagon tests for each child we found that whereas in the single test the blood glucose rose slowly with a peak at 30 min, in the combined test the peak was at 5 min. The mean peak values were similar (129 and 121 mg/100 ml). The mean peak insulin response in the single test was 70 muU/ml (at 2 min) as compared to 253 muU/ml (at 2 min) in the combined test. Our studies provide further evidence for a direct effect of glucagon on insulin release and that glucose preloading augments this effect, without relation to the concomitant blood glucose concentrations.