A lethal syndrome characterized clinically by growth retardation, progressive acrodermatitis, chronic pyoderma and paronychia, diarrhea, pneumonia, and abnormal behavior was observed in 17 related Bull Terrier pups. Median survival time was 7 months. Laboratory evaluation revealed non-degenerative neutrophilia, consistently low activities of serum alkaline phosphatase and alanine transaminase, and frequently, hypercholesterolemia. Lymphocyte blastogenic responses were decreased and there was dysgammaglobulinemia in pups in which quantitative studies of immunoglobulins were made. The mean of plasma zinc concentrations in 5 affected pups was significantly lower than the mean of age- and breed-matched controls. Pathologic findings included parakeratosis, hyperkeratosis, and superficial bacterial infections of the skin. There was severe reduction of lymphocytes in T-lymphocyte areas of lymphoid tissue. Bronchopneumonia and dilatation of the cerebral ventricles were found in most affected pups. Family studies indicated that the syndrome is inherited as an autosomal recessive trait. In spite of its similarities to lethal trait A46 in Black Pied Danish cattle and acrodermatitis enteropathica in man, oral or parenteral treatment with zinc failed to ameliorate the clinical signs of the syndrome.