The changes in the fecal flora and their correlation with the fecal drug concentrations were studied, employing 4 volunteers (healthy adult males) to whom 1 g of cefotetan was intravenously administered daily for 6 days. 1. In all of the subjects, the total counts of fecal organisms were slightly decreased 1 day after administration of cefotetan, then showed gradual increase, and recovered to the normal level on 8 days after the withdrawal of the drug. 2. Cefotetan caused drastic suppression of normal aerobic and anaerobic flora during the administration period, except streptococci that remained unchanged at all. The bacterial groups suppressed were bacteroidaceae, eubacteria, bifidobacteria, peptococcaceae, lactobacilli, enterobacteriaceae, lecithinase-positive clostridia, and staphylococci. Yeasts were found to increase during the administration period. 3. The changes in flora well correlated with the fecal level of the drug concentrations. This is in accordance with the in vitro antibacterial activity of the drug. 4. A period of more than 15 days was required after the withdrawal of cefotetan to recover the normal fecal flora. 5. Loss of body weight and diarrhoea were not observed in any of the subjects.