The receptor for interleukin-5 (IL-5) is composed of two distinct subunits, alpha and beta. The cDNAs that encode the mouse and human alpha-subunit were transfected into the mouse IL-3-dependent cell line, FDC-P1 expressing the mouse beta-chain intrinsically. The resulting transfectants became responsive to human and mouse IL-5, respectively. Using the mutant alpha-subunits, we found that the alpha-subunit as well as the beta-subunit participated in IL-5-mediated growth signal transduction. The FDC-P1 transfectants expressing the alpha-subunit which lacks its whole cytoplasmic domain did not respond to IL-5, though the interaction of the mutant alpha- and beta-subunits was not impaired. The transfectants expressing the alpha-subunit which lacks the C-terminal half of its cytoplasmic domain proliferated in the presence of IL-5. These results indicate that the transmembrane-proximal cytoplasmic portion of the alpha-subunit plays an important role in IL-5-mediated growth signal transduction.