Free-ranging African lion (Panthera leo) peripheral blood mononuclear cells (PBMC) were examined using flow cytometry and antibodies developed for use in the domestic cat to determine if phenotypic changes occurred in lion lymphocytes as a result of feline immunodeficiency virus (FIV) infection. The percentage of CD8 cells from lion peripheral blood was considerably lower than in the domestic cat. Lions with elevated levels of CD8+ cells were typically infected with FIV, similar to observations in the domestic cat. Antibodies against the α chain of the CD8 receptor (monoclonal antibody (mAb) 3.357) did not react consistently in all lions examined. Flow cytometric analysis determined that approximately 82 and 80% of the animals from Kruger and Hluhluwe-Umfolozi National Parks in South Africa reacted with the monoclonal antibody against the α chain of CD8 receptor, while only 17% of the lions in Etosha National Park in Namibia cross-reacted with the CD8α chain. There was no apparent correlation between FIV status and CD8α chain reactivity. The relative isolation of Etosha from the other two parks could explain the marked difference in CD8α chain expression and suggests that lions similar to other mammalian species demonstrate polymorphic expression of the CD8α chain (197). Keywords: African lion (Panthera leo), Monoclonal antibody, Cross-reactivity, CD8α polymorphism.