The aim of this experimental study was to investigate whether the intraperitoneal perioperative injection of 5-flurouracil (5-FU)--with or without the addition of interferon (INT)--influences colonic healing. We used 57 male Wistar rats which were subjected to anastomosis of the colon. Intraoperatively, the rats were randomised into one of three groups. The rats in the control group (group 1, n = 15) received a 0.9% NaCl solution; the rats in group 2 (n = 21), 5-FU (20 mg/Kg/day), and those in group 3 (n = 21), 5-FU (20 mg/Kg/day) plus INT (45,000 IU/Kg/day). These drugs were injected intraperitoneally during the operation and once daily for the next two days. The rats were sacrificed on post-operative days 3, 5 or 8. The rupture rate of the anastomoses was statistically significantly higher in groups 2 and 3, compared with the control group (P < 0.05); no differences were observed between groups 2 and 3. Abscess and adhesion formation were more marked in groups 2 and 3 than in the control group; however no differences were recorded between groups 2 and 3. The anastomotic bursting pressure was statistically significantly lower in groups 2 and 3 compared to the control group (P < 0.05), on post-operative days 5 and 8; however, no differences were measured between groups 2 and 3. Histologic evaluation also showed a more profound inflammatory response in groups 2 and 3, compared with group 1. In conclusion, the intraperitoneal, intraoperative administration of 5-FU hinders colonic healing in rats. The additional intraperitoneal injection of interferon does not seem to aggravate this adverse effect.