Signal transducer and activator of transcription 5A (Stat5a) and Stat5b, which share 96% homology, undergo receptor tyrosine kinase or G protein-coupled receptor-dependent phosphorylation in response to cytokines or growth factors, and then form homo- or heterodimers that translocate to the nucleus, where they initiate transcription. Activation of Stat5a via IL-2, IL-3, IL-7/ GM-CSF, erythropoietin, thrombopoietin and growth hormones influences proliferation, differentiation and apoptosis in lymphohematopoietic cells. Phos-phorylation of Stat5a at Ser127/Ser128 and Ser779 are contigent on ErbB-4-mediated activation of Stat5a. Activation of Stat5b via IL-2, IL-4, CSF-1 and growth hormones influences TCR signaling, apoptosis, adult mammary gland development and sexual dimorphism of liver gene expression. Stat5b is the major liver-expressed Stat5 form that has been shown to fuse with the retin-oic acid receptor a gene in acute promyelocytic leukemias (APLL). Stat5a/b null mice have severely impaired lymphoid development and differentiation.