Free malignant cells, which are frequently detected in the washing liquid from the peritoneal cavity before and after resection of human colorectal cancer, are suspected to cause recurrent peritoneal cancer. We carried out an experimental study to compare the prophylactic efficacy of washing the peritoneum with several anticancer drugs and the antiseptic povidone-iodine against the development of peritoneal carcinomatosis from colonic origin in rats and nude mice. The in vitro anticancer activity of a short, 15-minute exposure of pirarubicin, doxorubicin, 5-fluorouracil, cisplatin, mitomycin C, and 1% povidone-iodine was first evaluated by an MTT assay on DHD/K12/PROb rat and LS174T human colon cancer cells. For the in vivo experiments, BDIX rats were inoculated intraperitoneally (i.p.) with 1 x 10(6) DHD/K12/PROb cells followed by peritoneal scarring and a colocolic anastomosis. A 15-minute peritoneal washing with the anticancer drugs or povidone-iodine was then performed. Nude mice were i.p.-inoculated with 1 x 10(7) LS174T human cells and treated 2 hours later with i.p. pirarubicin. Only pirarubicin, mitomycin C, and povidone-iodine were fully cytotoxic in vitro against DHD/K12/PROb rat colon cancer cells. In contrast to pirarubicin and povidone-iodine, mitomycin C was not completely active against LS174Tcells. In vivo, pirarubicin cured DHD/K12/PROb-inoculated rats, even at the site of the peritoneal scarring and intestinal anastomosis. i.p. pirarubicin prevented the development of peritoneal carcinomatosis and liver metastasis in LS174T-inoculated mice. i.p. washing with pirarubicin cured 2-day-old, but not 7-day-old, peritoneal carcinomatosis in rats. Short exposure to i.p. pirarubicin is nontoxic and more active than povidone-iodine and other anticancer drugs in preventing the development of peritoneal carcinomatosis from colonic origin in rats and mice. The prophylactic effect of preoperative peritoneal washing with pirarubicin on the development of recurrent peritoneal cancer should be evaluated in a randomized clinical trial.