It is known that immunocompromised hosts show an enhanced susceptibility to microbial infections. Among these, viral infections represent a particular problem because of the lack of really efficient antiviral drugs. In the present report we have studied the effect of pharmacological immunosuppression with cyclophosphamide (CY) in virus infection in vivo, using Balb/c mice infected with influenza A virus (PR8). At the dose of 0.1 hemagglutinating units of viral inoculum, intranasal administration of PR8 virus caused the death of 50 to 60% of the animals within a period of 3-10 days. A single injection of CY (200 mg/kg) significantly increased mouse mortality to 90%, when PR8 virus challenge was performed 4 days after chemotherapy pretreatment. When the PR8 virus infection was performed at different times after CY-treatment, a similar appreciable effect was not observed. Severe alterations of some immunological parameters such as NK activity and analysis of lymphoid spleen cell subsets were related to the increased susceptibility to virus infection.