The toxicity and therapeutic index of cyclophosphamide (CP) in NIH Wwiss and (C57BL X DBA)F mice were affected by the addition of different antibiotics to the drinking water. Penicillin G or Vancomycin increased the rat and number of deaths that followed parenteral treatment with CP; however, penicillin or Vancomycin alone produced no deaths. Both penicillin and Vancomycin changed the normal composition of the gastrointestinal bacteria, thus increasing the antibiotic-resistant coliform bacteria. Neomycin or gentamycin, with or without penicillin or Vancomycin, reduced the number of deaths that followed parenteral treatment with doses of CP lethal to 35% of the animals (LD35). Neomycin and gentamycin reduced the number of coliform bacteria recoverable from the gastrointestinal tract. The doses of CP against L1210 murine leukemia. The combination of CP (LD35) with the aminoglycosides produced several long-term survivors, apparently because larger doses of CP can be used with few drug-related deaths.