The in vivo actions of human and fish insulin-like growth factor (IGF)-I have been compared to extend the understanding of the metabolism of IGFs in fish and to identify potential differences in their actions. The effects of acute administration of these proteins on the incorporation of glucose into muscle glycogen and leucine into liver protein in juvenile barramundi were investigated. In these in vivo metabolic assays, both baramundi IGF-I (bIGF-I) and human IGF-I (hIGF-I) increase the incorporation of D-[14C]glucose into muscle glycogen and [14C]leucine into liver protein. The distribution of radio-labeled human and barramundi IGF-I in the circulation and their uptake by tissue was also compared in juvenile barramundi (Lates calcarifer). Analysis of trichloroacetic acid-precipitable radioactivity in sequential samples following bolus injection of radiolabeled IGFs revealed that hIGF-I was degraded faster than bIGF-I. Neutral gel chromatography of these samples suggested that this difference is due to reduced affinity of hIGF-I, compared to bIGF-I, for the IGF-binding proteins (IGFBPs) present in the barramundi. Tissue uptake of [125I]-labeled hIGF-I and bIGF-I was similar except that [ 125I]bIGF-I uptake by the kidney exceeded that of hIGF-I. It is suggested that while some of the in vivo actions of IGFs in fish are conserved, functional differences between mammalian and teleostean IGFs exist, particularly with respect to their interactions with fish IGFBPs.