The mechanisms by which growth hormone (GH) initiates its effect on growth are largely unknown. In this report we examine the acute actions of GH with a focus on the intracellular signaling pathways leading from the cell-surface GH receptor into the nucleus, and culminating in the activation of specific target genes. We show that in vivo GH treatment leads to the rapid appearance of tyrosine-phosphorylated nuclear proteins and the equally rapid induction of c-fos and insulin-like growth factor I gene transcription. A model is proposed for a GH-activated intracellular signal transduction pathway.