To understand the molecular bases for cytoklne redundancy and pleiotropy, we have compared the Stat proteins activated in perlpheml blood lymphocytes (PBLs) by cytokines with shared and distinct actlons. interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat2 and Stat5 in pmactivated PBL. IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of simliar tyrosine-phosphoryiated motifs in the cytopiasmic domains of IL-2R5 and IL-7R that can serve as docking sites for Stat protelns. IL-13 induced the same complexes as IL-4, a flnding explained by our studies lmplicatlng lL-4R as a shared component of the receptors. These studies demon-strate that a single cytokine can activate different combinations of Stat proteins under different physloiogical conditions, and also indicate two mechanisms by which dlstlnct cytokines can activate the same Stat protein.