The somatomedin C/insulin-like growth factor I (SMC/IGF-I) response to human GH (hGH) therapy and the t1/2 of SMC/IGF-I after the cessation of hGH were determined in 15 children with GH deficiency. After 5 injections of hGH (0.1 U/kg), there was a significant increase in total SMC/IGF-I [from 0.27 +/- 0.06 to 1.19 +/- 0.17 U/ml (mean +/- SEM)]. Both the pretreatment SMC/IGF-I and the maximal SMC/IGF-I levels attained were correlated with chronological age and bone age. Body size, as indicated by height and weight, also correlated with pretreatment and maximal SMC/IGF-I levels. For both pretreatment and maximal SMC/IGF-I levels, there was a better correlation of SMC/IGF-I levels with bone age than with chronological age. While the correlation between height and the pretreatment SMC/IGF-I level was stronger, weight was a better predicter of the maximal SMC/IGF-I level. Maximal SMC/IGF-I levels were reached 18.8 +/- 2.9 h after the last hGH injection. The t1/2 for SMC-IGF-I after the attainment of maximal levels was 20.7 +/- 2.3 h, or 39.5 +/- 3.8 h from the last injection of hGH. The t1/2 of SMC/IGF-I determined in this way was longer than previous values reported from studies in the rat. The relatively long t1/2 of SMC/IGF-I which we observed may in part explain the success of present GH treatment regimens which involve every other day injections of hGH.