Failure of surgical treatment for gastrointestinal cancers is often caused by recurrence of the tumor in traumatized peritoneal surfaces. This study examined the effect of intraperitoneal administration of doxorubicin and recombinant tissue plasminogen activator (IT-PA), a fibrinolytic agent, on incidence and volume of postoperative tumor implants in peritoneal wounds. Prior to randomization, a surgical wound was created on the right parietal peritoneum of I 10 RDIX rats and 6 X lo5 DHD/K12 colon cancer cells were inoculated intraperitoneally (ip). The control group was given an intraperitoneal injection of saline. Five groups received 1 mgkg of ip doxorubicin at different times postoperatively: at the end of surgery (DO), 3 hr after surgery (D+3), postoperative day 1 (Dl), postoperative day 3 (D3), and postoperative day 7 (D7). In a second set of experiments, five groups of rats received, in addition to postoperative doxorubicin, 5 mgkg of intraoperative ip rt-PA. Incidence and volume of tumor implants in peritoneal wounds were assessed for each group 20 days after the tumor inoculation. All rats of the control group (incidence = 100%) developed tumor implants in peritoneal wounds. Mean (SD) volume was 16.2 (4.7) mm'. When administered at DO, D+3, and DI intraperitoneal doxorubicin reduced significantly the incidence and volume of tumor implants in wounds. Postoperative administration of doxorubicin at D3 and D7 did not affect significantly the incidence and the volume of tumor implants in peritoneal wounds. When rt-PA was administered intraoperatively, ip injection of doxorubicin at any postoperative timing decreased significantly the incidence and volume of tumor implants. In conclusion. ip doxorubicin administered before postoperative D3 may act on tumor cell implanted in peritoneal wounds. Delayed (D3, D7) ip administration of doxorubicin does not prevent the development of tumor implants in peritoneal wounds. Intraoperative administration of rt-PA may significantly increase the efficacy of delayed ip chemotherapy.