WC1, also known as T19, is the only unique gamma/delta T-cell differentiation antigen described to date other than the gamma/delta T-cell receptor. We present evidence that modulation of WC1 results in augmented proliferation of gamma/delta T cells. Immobilized IL-A29, a monoclonal antibody (mAb) specific for WC1, augmented proliferation of gamma/delta T cells in the autologous mixed leucocyte reaction (AMLR) as well as proliferation induced by either anti-CD3 or anti-CD5 mAb. In contrast, anti-CD5 mAb did not increase proliferation in the AMLR even though both CD5 and WC1 are members of the scavenger receptor cysteine-rich family of proteins and are expressed by bovine peripheral blood gamma/delta T cells. IL-A29 did not induce proliferation when assessed alone or in the presence of either phorbol myristate acetate (PMA) or interleukin-2. IL-A29 also did not induce detectable calcium mobilization when evaluated in the presence of monocytes, PMA, or following cross-linking of IL-A29 with anti-immunoglobulin antibody. We conclude that WC1 is a gamma/delta T-cell lineage-specific cell-surface differentiation antigen which is involved in activation of gamma/delta T cells using an as yet unidentified pathway.