Contrary to resting cells, neutrophils stimulated with concanavalin A resist inhibition by bifunctional N-hydroxysuccinimide esters. Con A prestimulated, cross-linker-treated cells released superoxide upon restimulation with PMA but did not respond to chemotactic peptides. Although rates of PMA-elicited NADPH oxidase activity were lowered by the treatment, the activation parameters, namely lag times of the reaction, were not altered. The protection by Con A against blockade by cross-linkers developed concomitantly to the activation of NADPH oxidase and indicated redistribution of cross-linker-susceptible cellular components responsible for activation with PMA. The identity of these components is discussed.