Lymphocytes obtained from patients with herpes simplex virus, type 1 (HSV) neutralizing antibodies were stimulated in vitro for 48 hr with heat inactivated HSV. Cell-free supernatant from these cultures was added to autologous or allogeneic HLA-DR-negative stromal (fibroblast) cells for 3 days. All stromal cultures were stained with monoclonal reagents by indirect immunofluorescence for Class I (B2) or Class II (HLA-DR) antigen expression. Supernatant from HSV-stimulated lymphocytes induced HLA-DR antigen on cultured stromal cells while supernatant from lymphocytes cultured in the absence of HSV antigen or from lymphocytes which did not proliferate in response to incubation with HSV antigen did not induce HLA-DR. The expression of Class II antigens induced by supernatant from HSV-stimulated lymphocytes was inhibited by the addition of purified antibodies to IFN.