Murine CD30 cDNA predicts a protein of 498 amino acids with homology to the TNF receptor family of proteins characterized by repeated cysteine-rich motifs in the extracellular domain. Murine CD30, although homologous to human CD30, has a 90 amino acid gap in an extracellular region that appears to be duplicated in human CD30. Murine CD30 cDNA was shown to be functional through the production of a soluble murine Ig fusion protein (CD30-Ig) that was active in binding to cells that expressed CD30 ligand. CD30-Ig also served as an immunogen for the production of hamster anti-mouse CD30 mAbs, which recognized both CD30 expressed by murine lymphocytes and CD30 expressed by cells transfected with murine CD30 cDNA. CD30 mRNA is highly expressed in the thymus and in activated spleen cells, but not in other tissues tested. In anti-CD3-activated spleen cells, CD30 ligand is expressed primarily by CD4+ T cells, with peak expression at days 1 and 2, whereas CD30 is expressed primarily by CD8+ T cells, with peak expression on days 4 and 5. Stimulation of CD30 by plate-bound anti-CD30 directly signaled for IL-5 but not IFN-gamma production by CD30+ CTL lines. These studies demonstrate that CD30 directs cytokine secretion and suggest that CD30 signaling may be pivotal in the pattern of cytokine production by T cells.