Receptor-mediated activation is accompanied by phospholipid metabolism and by calcium fluctuation resulting in a chemiluminescence (CL) response in the neutrophil. This pathway involves activation of protein kinase C (PKC) and the NADPH oxidase. Artificial stimulants such as phorbol esters, specifically 12-O-tetradecanylphorbol-13-acetate (TPA), circumvent the receptor-mediated pathway and activate PKC resulting in a measurable CL response. Neutrophils from feline leukemia virus (FeLV) exposed cats were tested for their ability to generate a TPA-induced CL response. As compared to the non-FeLV-exposed specific-pathogen-free (SPF) control cat neutrophil CL responses, both viremic and nonviremic FeLV-exposed cats showed significant decreases in their CL responsiveness. Neither ultraviolet light-inactivated FeLV (UV-FeLV) nor protein components (FeLV-p15E and FeLV-p27) caused a significant decrease in the CL responses of the SPF cat neutrophils. The suppressed TPA-induced CL response from FeLV-infected cats may involve an intracellular mechanism not affected in vitro by exposure of the neutrophil to the virus or viral components.