Pokeweed antiviral protein (PAP) inhibits HIV-1 replication in HIV-1 infected CD4+ cells and PAP targeted to CD4+T-cells by conjugation with monoclonal antibodies (mAb) against CD4 is approximately 1000 times more potent than non-conjugated PAP. Furthermore, PAP-antiCD4 inhibits HIV-1 production in seropositive patients' CD4+ T-cells activated with mAb to CD3 which was found to be the most potent means to activate HIV-1 production. These findings, together with previous observations that PAP-mAb conjugates have an in vivo plasma half-life of about 30 times that of non-conjugated PAP, suggest that PAP-antiCD4 may be a useful therapy in HIV-infected humans. Additionally, because PAP is known to have antiviral activity against several other human viruses, PAP-mAb conjugates may also have clinical potential for treating other viral diseases.