Somatomedin activity as determined by the stimulation of [3H]thymidine incorporation into chick embryo fibroblast DNA, was measured in extracts of sera from genetically small mice. Somatomedin activity was low in the sera from growth hormone deficient mice [Snell (dw/dw), Ames (df/df), and little (lit/lit)] whereas Somatomedin activity was normal in serum from the pygmy (pg/pg) mouse, a mutant proposed as a model for growth hormone resistance. GH treatment of the Snell mouse resulted in an increase in somatomedin activity to normal levels.