Gastrointestinal malignancy may spread to peritoneal surfaces in the absence of lymphatic or hematogenous metastases. To treat peritoneal carcinomatosis, a uniformly lethal disease process, extensive cytoreductive surgery and i.p. chemotherapy were combined. Early postoperative i.p. chemotherapy was instilled in the first few days after the surgical procedure in an attempt to treat anatomic sites that would be sealed off by postoperative adhesions. Mitomycin C was given on the first postoperative day at two doses, 10 and 12 mg/m2. 5-Fluorouracil was given on postoperative days 2-5 at 15 and 20 mg/kg, respectively. Median area under the curve ratio i.p./i.v. was 117 for 5-fluorouracil and 21.6 for mitomycin C. Elevated intraportal levels of drug were observed for i.p. 5-fluorouracil but not for mitomycin C. The marked pharmacokinetic advantage of postoperative i.p. suggests that this treatment strategy should be considered in a clinical trial in patients at risk for progression of peritoneal carcinomatosis.