Chlorite-oxidized amylose (COAM), polyinosinic-polycytidylic acid [poly(I:C)], and combinations of the two drugs were evaluated for their interferon-inducing properties and their ability to protect mice against rabies infection. Post-exposure administration of one or two doses (100 mug each) of poly(I:C) significantly protected mice against rabies infection. Pretreatment of mice with COAM 3 h before poly(I:C) stimulation resulted in an enhancement of the interferon response. However, the increased interferon titers were not reflected by increased protection against rabies infection over that achieved with poly(I:C) therapy alone. Therapy with COAM alone did not protect mice against rabies but, rather, was associated with enhanced mortality.