Feline leukemia virus (FeLV) is a retrovirus with immunosuppressive properties. The mechanism(s) of immunosuppression is unknown. Calcium has been shown to be a second messenger in cellular activation and regulation. This study was designed to determine whether FeLV alters intracellular free calcium (IFC) levels in an FeLV-infected feline lymphoid cell line. Control cells and FeLV-infected cells were exposed to Concanavalin A, formyl-L-methionyl-L-leucyl-L-phenylalanine, and leukotriene B4. The basal IFC and post-stimulation IFC levels were recorded using Fura 2 AM and a luminescence spectrometer. Data collected indicate that FeLV-infected cells have a higher basal level of IFC and a reduced amount of increase in IFC after stimulation when compared to the control cells. The results would seem to indicate retrovirus-mediated interference occurring in the intracellular calcium signaling process.