This study evaluates whether preoperative administration of flurbiprofen alters the levels of immunoreactive bradykinin (iBK) peripherally released into inflamed tissue. Thirty-six patients were randomly treated on a double-blind basis with either flurbiprofen (100 mg) or placebo before the surgical extraction of impacted third molars. Microdialysis probes were implanted into the surgical site and dialysates, and subjective pain reports were collected every 15 minutes for 4 hours after surgery. Tissue levels of iBK were measured using a radioimmunoassay. Preoperative administration of flurbiprofen significantly reduced patients' reports of pain from 120 to 240 minutes after surgery and blocked the peak increase in tissue levels of iBK (135 to 150 minutes after surgery). Although these results indicate that flurbiprofen has an “antibradykinin” effect, the analgesia both preceded and persisted beyond the inhibition of iBK levels. Accordingly, an antibradykinin effect may only partly contribute to flurbiprofen analgesia. The data are consistent with the hypothesis that prostaglandins contribute to the peak release of iBK owing to the potent inhibition of prostaglandin synthesis by flurbiprofen, but other yet unidentified mediators are also required for the sustained release of this inflammatory mediator into the surgical field.