With the aid of a recently developed commercially available radioimmunoassay for Somatomedin-C (Sm-C) we measured the Sm-C levels in 38 controls, 24 untreated acromegalics, 45 inactive acromegalics and five pituitary dwarfs. With the exception of the dwarfs, the age and sex distributions for the various groups were similar. In inactive acromegalics the basal GH level (calculated as the mean of four blood samples taken during the day) was less than 5 mU/l; it was depressed to, or less than, 2.5 mU/l during the 100 g oral glucose tolerance test. The mean Sm-C level found for control subjects was 20.4 +/- 5.1 nmol/l and for untreated patients 85.6 +/- 25.7 nmol/l (mean +/- SD, P less than 0.001). The mean Sm-C level for inactive patients who had undergone surgery and invariably showed a normalized paradoxical reaction to TRH was 18.2 +/- 7.1 nmol/l (NS) vs 16.1 +/- 8.2 nmol/l (NS) for those who underwent surgery plus postoperative pituitary radiation therapy. Only one out of 45 inactive acromegalics exhibited an increased Sm-C level. The Sm-C levels correlated significantly not only with the log GH levels (r = 0.82) but also with the fasting insulin/glucose ratio the integrated incremental insulin levels, the maximal insulin increase and the integrated glucose levels during the oral glucose tolerance test as well as the 24-h urinary excretion of calcium and hydroxyproline.(ABSTRACT TRUNCATED AT 250 WORDS)