Activation of protein kinase C by a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was shown to stimulate the respiratory burst in normal cat neutrophils. Neutrophils from feline leukemia virus (FeLV)-exposed viremic and nonviremic cats had significant suppression of their respiratory burst when stimulated with TPA. The addition of whole ultraviolet light-inactivated FeLV and FeLV proteins to normal cat neutrophils produced no significant suppression of the respiratory burst. These data suggest two possible mechanisms for suppression. The first is partially due to viral alterations of the neutrophil as seen in viremic cats, but, because exogenously applied FeLV or FeLV proteins had no effect on the respiratory burst, an additional mechanism is present. The second mechanism may be caused by a latent FeLV infection residing in nonviremic cat bone marrows which alters their immune system, resulting in immunosuppression.