Effector mechanisms responsible for protection against ectromelia virus (EMV) including antiviral activity of non-immune macrophages, cytotoxic T cells, antiviral antibody, delayed footpad reaction to viral antigen and interferon induction after viral infection were depressed in BALB/c mice bearing syngeneic Meth A tumors. The degree of viral growth correlated well with the depression of delayed footpad reaction, antibody production and interferon induction. But a control level of these elements could be obtained by pretreatment of tumor-bearing mice, with PSK Cytotoxic activity may not be the principal effector, since cytotoxicity was induced in both normal and tumor-bearing mice to almost the same extent but an explosive viral growth was observed only in the latter. These results suggest that PSK was responsible for restoring the depressed antiviral protective immunity to normal levels in tumor-bearing animals.