Current reports suggest a beneficial effect of long-term metronidazole ( MTZ ) therapy in Crohn's disease. Since Crohn's disease is associated with a higher risk of bowel cancer and long-term MTZ has been shown to have a tumorigenic potential in rodents and a cocarcinogenic effect in experimental colon cancer, more studies are required to explore this area. Eighty-one rats were divided into four groups. Group A served as a control, groups B and C were given MTZ in their food (50 mg/kg/day). In groups C and D, a 3-cm colonic segment was isolated and brought out as a blind loop fistula. All animals received 20 weekly sc doses of 1,2-dimethylhydrazine (DMH) and were killed 25 weeks after the first injection. The mean number of colon tumors per animal (+/- SEM) in MTZ groups B (1.65 +/- 0.29) and C (2.57 +/- 0.38) were higher than A (1.44 +/- 0.3) and D (1.18 +/- 0.21), but the increase was only significant for group C over groups A and D (P less than 0.05) and group B (P = 0.06). The mean number of tumors per animal in the isolated loop of group C (0.95 +/- 0.28) was similar to group D (0.68 +/- 0.16) P = 0.41, but the mean number of tumors in the functioning colon of group C (1.62 +/- 0.25) was higher than group D (0.5 +/- 0.12) P less than 0.001. These findings suggest that long-term MTZ increased the number of colon tumors per rat in the DMH model but a statistical significance (P less than 0.05) was only noted in the MTZ and surgery group.(ABSTRACT TRUNCATED AT 250 WORDS)