In the present investigation the clinical effect of treatment with metronidazole or sulfasalazine on patients with Crohn's disease was related to changes in the fetal flora. The clinical effect was evaluated by Crohn's Disease Activity Index (CDAI) and serum(s)-orosomucoid value. Twenty patients were included. All patients were untreated for at least 1 month before entrance to the study. None had any previous history of bowel resection. The results of CDAI, s-orosomucoid values, and the bacterial counts obtained at the start were compared to those at the end of treatment. Only changes of more than 33% of the CDAI or s-orosomucoid and changes of more than 3 log, i.e. 99.9%, of the bacterial counts are considered significant. Seventeen patients had a treatment period of 1-4 months. Their total counts of aerobic and anaerobic bacteria were unchanged. In 6 of 17 patients the Bacteroides counts decreased by more than 99.9%. In 13 of the 17 patients there was a dependence between the Bacteroides counts and s-orosomucoid values (P = 0.05) and in 9 out of 17 patients between the Bacteroides counts and CDAI (P less than 0.05). The use of CDAI and s-orosomucoid as measures for disease activity is discussed, and so are the modes of action of the two drugs in relation to the present results and the etiology and pathogenesis of Crohn's disease.