Administration of corticosteroids, aspirin, or indomethacin induces marked inhibition of adherence of polymorphonuclear leukocytes (PMNLs) in vitro. The effects of three newer nonsteroidal anti-inflammatory agents on PMNL adherence were defined. Adherence of PMNLs after passage through a nylon-wool column was measured in normal volunteers who had ingested a single tablet of 300 mg of ibuprofen, 300 mg of fenoprofen, or 200 mg of sulindac. Adherence was significantly decreased from baseline at 4 hr after ibuprofen or fenoprofen was taken, remained suppressed at 24 hr, and returned to normal at 48 hr. Sulindac mildly inhibited PMNL adherence 48 hr after drug ingestion. Inhibition of adherence with ibuprofen and fenoprofen also occurred after incubation of control PMNLs with plasma specimens from volunteers 4 and 24 hr after drug administration, a result suggesting a partially plasma-mediated factor. Zymosan-induced augmented adherence was also inhibited by pretreatment in vitro with ibuprofen at a concentration of 25 micrograms/ml and fenoprofen at 50 micrograms/ml.