In supernatants of mixed mouse spleen cell cultures established for 4 days, a species-specific inhibitor of virus replication with a broad antiviral spectrum was found. The inhibitor was destroyed by trypsin, was nondialyzable and acid labile, and was not neutralized by antibody to mouse L cell interferon. This indicates that in mixed lymphocyte cultures a type II interferon is made that has no immunological relationship with "fibroblast" interferon. This leukocyte product was shown to protect mouse hepatitis viruses. It is suggested that lymphocyte interferon may collaborate with macrophages in host defense against viruses, as a mediator of cellular immunity.