We report mycobacterial granulomatous inflammation in the ulcerated caecum of rats that received indomethacin. Two groups of male rats were treated with dietary indomethacin 3 mg/kg/day or untreated diet for 3 weeks. Six out of 8 indomethacin treated rats showed both ulceration and inflammation of the caecal mucosa. Two of the rats showing caecal ulceration also showed distinct granulomatous inflammation of the caecal mucosa and acid-fast bacilli were identified within granulomata. None of the other indomethacin treated or control rats contained acid-fast bacilli within caecal tissue sections but they were present, in the same sections, within the lumen of most rats in both groups. Polymerase chain reaction analysis identified the mycobacterial 65 kDa GroEL gene within control and granulomatous caecal tissue. In a repeat of indomethacin administration to a third group of rats, culture of both non-granulomatous caecal tissue (containing histologically identified luminal acid-fast bacilli) and faecal samples for mycobacteria was negative.