The primary structure of the somatomedins (SM) IGF-I and IGF-II has been known for some years. Both from isolation of the SMs from plasma and from the study of cDNAs it has become evident that there are more SMs, needing further study. In plasma the SMs are present in larger molecules of two size-classes: 150 kD and 40 kD, behaving as specific SM-binding proteins. The possibility that such protein classes are heterogeneous and also contain precursor molecules undergoing proteolytic processing is considered. The somatomedin genes are discontinuous and span large regions of the human genome.