Control of colon cancer depends, in part, on intact immune defense mechanisms. Since opiates are known to affect some components of immune function, this study was conducted to determine the effect of high-dose subcutaneous morphine sulfate and of low-dose intrathecal morphine on the postoperative growth of metastatic colon cancer. Five groups of 15 Fischer 344 rats were given intraportal injections of colon cancer cells as follows: group 1, control; group 2, daily subcutaneous injections of 20-mg/kg morphine the day before and for 2 days after colon cancer cell inoculation; group 3, daily subcutaneous injections of saline; group 4, daily intrathecal injections of 20 micrograms of morphine; and group 5, daily intrathecal injections of saline. There was a significant decrease in the hepatic tumor burden in group 2 compared with groups 1 and 3 and a significant increase in the hepatic tumor burden in groups 4 and 5 compared with group 1. This study demonstrates that intermittent injections of a narcotic may decrease the growth of tumor cells that gain access to the circulation during a surgical procedure. In addition, the results support the concept that tumor cells entering the circulation during a vulnerable period of postoperative immunosuppression are more likely to survive as metastatic tumor.