Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.