The effect of GH administration (5 mg twice daily for 5 days) on the serum concentration of insulin-like growth factors I and II (IGF I and IGF II) was compared in GH-deficient subjects during a period of fasting and a period of normal food intake. Before treatment with GH, the mean concentration of IGF I was 35.2 +/- 7.5 ng/ml. After 5 days of GH treatment in the fed state, IGF I increased nearly 10-fold to 317.4 +/- 55.9 ng/ml (P less than 0.001 vs. pretreatment value). During fasting, identical treatment of the group resulted in only a modest increase of IGF I to 81 +/- 23 ng/ml (P less than 0.001 vs. fed state response). The serum concentration of IGF II before therapy was reduced to only 174 +/- 37 ng/ml. With GH given in the fed state, IGF II increased to 793 +/- 171 ng/ml. These data suggest that IGF II, like IGF I, is GH dependent and, hence, a somatomedin. GH therapy in the fasted state increased IGF II to 437 +/- 70 ng/ml (P = 0.05 vs. fed state response). In a second study, six normal subjects were fasted for 72 h. The integrated serum IGF I concentration (24 samples/subject) decreased 42% by the third day of fasting; IGF II decreased 27% during the same period. The data from both studies are consistent with the conclusion that the metabolic milieu of fasting inhibits IGF secretion in man. IGF I appears to be affected more than IGF II.