The treatment of human peripheral blood mononuclear cells (PBMC) with micromolar concentrations of SV-IV, a major protein secreted from the rat seminal vesicle epithelium, promotes in this cell population a marked cytotoxic activity against the Raji lymphoblastoid cell line. This activity is apparently due to cell-to-cell contact interactions. The expression of HLA DR on Raji cells has a modulatory effect on the SV-IV-induced cytotoxic activity. The experimental evidence strongly suggests that the cytotoxic effector cells are functionally activated NK cells.