Although chemotherapeutic agents are widely used in the treatment of cancer, few experimental data are available on their effects on host N metabolism. We studied the effects of a single intraperitoneal (IP) injection of cyclophosphamide ([CYP] 120 mg/kg), 5-fluorouracil ([5-FU], 50 mg/kg), cisplatinum ([CDDP], 5 mg/kg), or methotrexate ([MTX], 30 mg/kg). N balance was studied for 6 days following chemotherapy in healthy rats (n = 40) and in rats bearing Morris Hepatoma 7777 ([MH7777] n = 40) in a situation comparable to that of human cancer (tumor burden < 0.2% of body weight, moderate anorexia, and weight loss). In healthy rats, all drugs induced transient body weight loss, anorexia, and poor N balance. At day 6 posttreatment, all animals had resumed normal feed intake and positive N balance except CDDP-treated rats, which showed continued weight loss and poor N balance. CDDP and MTX exhibited antitumor activity; however, CDDP induced diarrhea in six of eight tumor-bearing rats. Drug-induced anorexia was more severe in tumor-bearing than in healthy treated rats. N balance was more severely decreased in MH7777-bearing rats than in healthy treated animals in response to 5-FU (159 +/- 36 v 273 +/- 27 mg N/2 d) and MTX (-66 +/- 36 v 153 +/- 37 mg N/2 d) at days 3 to 4 postinjection. These results establish the presence of drug-specific effects on host N balance and the existence of a drug-tumor interaction for N metabolism in the tumor-bearing host.