We have isolated the human cDNA homologue of a mouse helper T-cell-specific cDNA sequence, called P600, from an activated human T-cell cDNA library. The human cDNA encodes a secreted, mainly unglycosylated, protein with a relative molecular mass of approximately 10,000. We show that the human and mouse proteins cause extensive morphological changes to human monocytes with an associated up-regulation of major histocompatibility complex class II antigens and the low-affinity receptor for immunoglobulin E (Fc epsilon RII or CD23). In addition, they stimulate proliferation of human B cells that have been activated by anti-IgM antibodies or by anti-CD40 monoclonal antibodies presented by a mouse Ltk- cell line transfected with CDw32. Furthermore, the human protein induced considerable levels of IgM and IgG, but no IgA production, in cultures in which highly purified human surface IgD+ or total B cells were cocultured with an activated CD4+ T-cell clone. Based on these findings, we propose that this immunoregulatory protein be designated interleukin 13.