The importance of reactive oxygen species (ROS) in neutrophil (PMN)-mediated injury to host tissues has been strongly implicated in a number of animal models. Peculiarities of the laboratory rat PMN, including an apparent paucity of superoxide release, prompted us to examine disparities in the respiratory burst between human and rat PMNs. Using isolated PMNs, we examined oxygen consumption, superoxide release, nitrate/nitrite release, and dihydrorhodamine (DHR) oxidation in response to an array of soluble stimuli. Our findings confirm that intact rat PMNs release little superoxide in comparison to human PMNs when primed and activated by soluble stimuli. For example, PMA-activated human PMNs released superoxide at 10.1 +/- 2.7 times the rate of rat PMNs (P < 0.01). However, measurements of oxygen consumption, cell-associated oxidant production (by DHR oxidation) and release of superoxide from electroporated cells suggests that rat PMNs generate oxidants at rates equivalent to human PMNs but preferentially release them in an intracellular compartment. Implications for the study of PMN-mediated oxidant injury in animal models are discussed.