The present study of metronidazole in perineal Crohn's disease includes 26 patients, and is composed of 17 of 21 patients who were previously reported and 9 additional consecutive patients. The course of these patients was evaluated to determine if the drug could be reduced or stopped, whether or not it continued to be effective for prolonged periods, and what long-term side effects were encountered. Dosage reduction was associated with exacerbation of disease activity in all patients, but in all, the perineal manifestations of disease healed promptly when the full dosage of metronidazole was reinstituted. The drug could be successfully discontinued in only 28% of those in whom cessation was attempted; in those patients whose perineal disease worsened with cessation of therapy, rapid healing was achieved if the drug was reintroduced. Sixteen patients received metronidazole for at least 12 mo including 7 for 18-36 mo. Eight of these 16 patients, including 4 on and 4 off the drug, remain healed; the other 8 patients had advanced healing. The only major side effect observed was paresthesias. These occurred in 50% of the patients and developed in the patients at a mean of 6.5 mo after the onset of treatment. They appeared to be dose related and nonprogressive but tended to persist for prolonged periods even after discontinuance of the drug.