The acute metabolic effects and receptor binding of insulin-like growth factors (IGFs) I and II were studied in human adipose tissue. The IGFs inhibited fat cell glycerol release and stimulated adipocyte 3-O-methylglucose transport and adipose tissue glucose oxidation as effectively as did insulin, but the biological potencies of the IGFs, on a molar basis, were 600-1000 times less than that of insulin. The insulin dose-response curve for antilipolysis gradually shifted to the left in the presence of submaximally and maximally effective IGF-I concentrations, whereas no additive response was found when fat cells were incubated with maximally effective concentrations of insulin and the IGFs. Adipocyte [125I]IGF-I and -II binding was low and was not inhibited by excess unlabeled IGF. In contrast, IGF-I inhibited [125I]insulin binding with a molar potency 1600 times lower than that of native insulin. In adipose tissue segments obtained from patients with untreated noninsulin-dependent diabetes mellitus, IGF-I and insulin inhibited glycerol release in a normal way. Conversely, neither insulin nor IGF-I increased the rate of glucose oxidation significantly above the nonhormone-stimulated level. We conclude that human fat cells lack specific cell surface IGF-binding sites. However, the IGFs definitely produce acute insulin-like effects in the human adipocyte, which seems to be mediated via the insulin receptor.