The circulating concentrations of insulin-like growth factor I (IGF-I) and immunoreactive aminoterminal propeptide of type III procollagen (PIIINP) were measured in 12 children with short stature (8 GH deficient and 4 non-GH deficient) before and after 1 week, 5 weeks, and 3, 6, and 12 months of treatment with biosynthetic hGH. Seven children had a growth response (increase in relative growth velocity greater than 1.5 SD during the initial 6 months) to GH therapy (responders), whereas 5 failed to respond (nonresponders). No relationship was found between the pretreatment plasma IGF-I levels or their changes during therapy and the growth response. Serum PIIINP levels increased considerably in all but 3 children, after as little as 1 week of GH administration. After 5 weeks, all responders had an increase in their serum PIIINP concentrations of 40% or more, whereas the nonresponders had less or no increments. There was a close correlation between the GH-induced increase in serum PIIINP levels at 5 weeks and growth velocity after 6 months of GH therapy (r = 0.77; P less than 0.01). The correlation was even stronger with the growth velocity at 12 months (r = 0.83; P less than 0.001). The serum PIIINP response to short-term GH administration could be an early predictor of the growth response to long-term GH therapy. In contrast to plasma IGF-I, the PIIINP response may be useful both in GH deficient and non-GH deficient children.