Flavonoids are naturally occurring plant compounds that have been demonstrated to possess a variety of anti-inflammatory effects. We studied the effects of flavonoids on three aspects of neutrophil function that are commonly considered to be associated with inflammation: the release of lysosomal enzymes, the chemiluminescence (CL) response, and the production of superoxide anion. Quercetin and eight other flavonoids at a 10(-5)M concentration inhibited the neutrophil CL response to opsonized zymosan particles by approximately 60% or more. In contrast, the release of lysosomal beta-glucuronidase from neutrophils stimulated with opsonized zymosan was only inhibited by two flavonoids, quercetin and chalcone, and only at concentrations of 1.5 X 10(-4)M to 2 X 10(-4)M. Quercetin also inhibited the generation of superoxide anion by neutrophils but to a lesser degree than its effect on CL. The present studies demonstrated that certain flavonoids are not uniformly active in inhibiting neutrophil CL, beta-glucuronidase release, or superoxide generation. The effects of flavonoids on neutrophil functions probably depend on many variables including the response measured, the activating stimulus, and specific flavonoid structural features.