The concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) and their binding proteins in serum were measured in 10 GH-deficient patients before and after a single 6-IU injection of GH. Serum IGF-I concentrations were initially low, increased significantly by 8 and 24 h, and decreased to pretreatment levels 48 and 72 h after GH administration. Serum IGF-II concentrations also were low initially and did not increase by 8 and 24 h, but were, however, significantly higher 48 and 72 h after GH administration. In GH-deficient patients before GH administration, binding of IGF-I or IGF-II to serum proteins was restricted primarily to proteins of 50K mol wt. Little or no binding to proteins of 150,000 mol wt was found. By 8 and 24 h after GH injection, IGF-I, but not IGF-II, bound primarily to a protein(s) of 150K mol wt, as in normal subjects. IGF-II remained bound to a 50K mol wt protein. By 48 and 72 h after administering GH, however, the binding pattern was reversed, and IGF-II, but not IGF-I, bound predominantly to a protein(s) of 150K mol wt. Our data demonstrate both a temporal dissociation in the responses of IGF-I and IGF-II to GH and a similar temporal dissociation in the binding of IGF-I and IGF-II to the large mol wt (150K) binding protein. This dissociation, particularly the latter, may provide a means for better characterization of protein fractions in binding IGF, particularly in terms of specificity.