Human neutrophils stimulated with either latex particles or opsonized zymosan exhibited equivalent rates of net oxygen consumption as well as hydrogen peroxide release. The quantity of superoxide (O2-) detected in latex-stimulated neutrophils was less than 2% of that seen with opsonized zymosan stimulation, and only several-fold greater than that of resting cells. The failure to detect O2- in the latex-stimulated neutrophils was due neither to latex acting as a O2- scavenger nor to its interference with the O2- -forming system of the neutrophil. An intracellular site of O2- generation could not be demonstrated. NADPH oxidase activity in cells exposed to latex particles was only 10% of that seen in cells comparably activated with opsonized zymosan. Latex particles have the unusual property of stimulating the respiratory burst of the human neutrophil without the extracellular release of O2-. The potential physiologic importance of this finding is discussed.