A line of transgenic mice carrying a chimeric gene composed of human insulin-like growth factor I (IGF-I) coding sequences fused to the mouse metallothionein I promoter was generated to study the effects of chronically elevated exposure to IGF-I. Mice in this line overexpress IGF-I in most tissues studied and have circulating IGF-I levels 1.5 times the normal value. This results in a growth response manifested by a 1.3-fold increase in weight as a result of selective organomegaly without an apparent increase in skeletal growth. In addition, expression of the endogenous GH and IGF-I genes is inhibited. These results are consistent with IGF-I playing an important role in the control of somatic growth.