Unlike other nonsteroidal antiinflammatory agents, benoxaprofen has only minor antiprostaglandin synthetase activity. This property may explain the lack of gastric irritation seen in animal studies. To evaluate gastric irritation in man, benoxaprofen was compared with aspirin, naproxen, ibuprofen, sulindac, and indomethacin by measuring fecal blood loss with chromium-51 tagged red blood cells in randomized double-blind crossover and parallel studies. Benoxaprofen produced significantly less blood loss than aspirin, naproxen, or indomethacin, and less blood loss than ibuprofen or sulindac. Benoxaprofen also caused the fewest gastrointestinal complaints.