Limiting degradation of collagen during the initial phase of wound healing is expected to improve postoperative intestinal strength and thereby decrease chances for anastomotic dehiscence. We studied the influence of four nonsteroid anti-inflammatory drugs on the healing of intestinal anastomoses in rats, with special regard to changes of collagen levels around the anastomoses. Four experimental groups of 20 rats each received daily oral doses of piroxicam, ibuprofen, aspirin, or indomethacin and were compared with a control group. Animals were sacrificed 3 or 7 days after operation. Both morbidity and mortality rate in the experimental groups were high. Collagen, measured as hydroxyproline, levels in anastomotic and adjoining 1-cm intestinal segments were compared with concentrations in control segments resected during operation. After an initial decrease on day 3, hydroxyproline concentrations increased on day 7. In the colon the lowering of hydroxyproline concentrations, which was more pronounced than in the ileum, was significantly reduced by administration of piroxicam and ibuprofen, both in the anastomosis and its proximal segment. On day 7, the increase of hydroxyproline concentrations in the ileum was inhibited by administration of anti-inflammatory drugs. It is concluded that nonsteroidal anti-inflammatory drugs may limit postoperative degradation of collagen in colonic anastomoses, but at the same time may increase the rat's susceptibility to surgical infections.