The acute somatomedin (SM) response to GH therapy has been examined in 21 GH-deficient children using a placental membrane radioreceptor assay (RRA) which measures a variety of SMs and a RIA specific for SM-C and insulin-like growth factor I (IGF-I). Plasma for determination of SM peptide content was obtained before initiation of therapy and 13 h after each of four daily injections of GH (0.1 U/kg). An additional SM determination was performed after 6 weeks of GH therapy (0.1 U/kg, three times per week) in seven of the subjects. RRA and RIA SM determinations were performed on the same acid-chromatographed sample and were compared to an acid-chromatographed pooled plasma standard. The 4 days of GH therapy resulted in an increase in SM levels from 0.39 +/- 0.24 to 1.18 +/- 0.62 (+/- SD) U/ml, determined by RIA. A single injection of GH resulted in a significant rise in plasma SM levels, measured by either RRA or RIA (P less than 0.001). Subjects who responded poorly to two injections of GH also had low SM levels after 4 days and even after 6 weeks of GH therapy. The RRA resulted in consistently higher value than the RIA. This difference was even greater when results were compared to a pure IGF-I/SM-C standard. The SM peptide contents determined by RRA and RIA were strongly correlated, not only for the group, but also among the determinations for each individual subject. However, the consistently higher values observed when the SM peptide content was measured by RRA compared to that measured by RIA and the variability in the RRA to RIA ratio among individual subjects suggest that the IGF-I/SM-C RIA measures only one of a number of GH-dependent SM peptides.