The purpose of this series of experiments was to determine the effect of various types of immunosuppressive treatments (cyclophosphamide, infectious bursal disease virus [IBDV], chicken anemia virus [CAV], and combination infection with IBDV and CAV) on susceptibility of chickens to challenge with avian polyomavirus. In the first experiment, chickens were chemically bursectomized with intraperitoneal injections of cyclophosphamide; in the second study, chickens were orally inoculated with IBDV; in the third study, birds were intramuscularly inoculated with CAV; and in the final study, birds were inoculated with both IBDV and CAV. In all experiments, chickens were challenged with 10(4.7) tissue culture infective doses of polyomavirus intraperitoneally. Only chemically bursectomized chickens developed lesions similar to those found in the naturally occurring multisystemic fatal form of polyomavirus infection seen in psittacine nestlings, including hepatic necrosis and large pale intranuclear inclusions.