Abstract: Two adult snow leopards (Panthera uncia), male and female, both with vaccinations current, became infected with feline panleukopenia virus (FPV) at the Blank Park Zoo, Des Moines, Iowa, in late 1988. Clinical signs included weakness, hemorrhagic feces, fever, seizures, and nasal discharge. Blood analysis revealed severe lymphopenia and mild anemia. A positive enzyme-linked immunosorbent assay (ELISA) test for FPV on fecal contents from the male leopard confirmed the diagnosis. In spite of intensive therapy, both animals died. Necropsy of the female, which survived for 1 wk after onset of signs, revealed intestinal crypt necrosis, pulmonary consolidation, necrotizing laryngitis, and diffuse lymphoid depletion. The male leopard, which lived 3 wk after onset of illness, had similar enteric and lymphoid lesions. In addition, there was a severe interstitial pneumonia, with syncytial cells containing eosinophilic intracytoplasmic inclusion bodies. Ultrastructural characteristics of these inclusions featured tubular structures consistent with a paramyxovirus. Although repeated virus isolation attempts from the affected lung were negative, polyclonal and monoclonal fluorescent antibody tests were strongly positive for canine distemper virus (CDV). Frozen paired sera from each leopard demonstrated very high acute and convalescing titers to FPV; both animals also seroconverted to CDV, with titers in the male leopard higher than those in the female. Additional tests for toxoplasmosis, feline infectious peritonitis, feline rhinotracheitis, feline calicivirus, feline leukemia, canine parainfluenza, and bovine respiratory syncytial virus were all negative. The neurologic signs present in these leopards remained unexplained, but may have been attributable to CDV infection. A feral cat trapped on zoo property had feces positive for FPV by ELISA. Although the specific contributions of FPV and CDV toward the development of this case are unknown, it is likely that initial FPV-induced immunosuppression allowed the subsequent development of CDV in these snow leopards. The likelihood that initial FPV infection came from feral cats underscores the importance of feral animal control on zoo premises.