AbstractAn anaplastic, metastatic subline of the Dunning rat tumor was exposed to non‐cytodestructive doses of the cellular differentiation agents dimethylsulfoxide and difluoromethylornithine. Copenhagen rats hosting prostate tumors were evaluated by comparing solid tumor growth resulting from injection of treated cells with solid tumor growth of untreated control cells. Results showed significantly slower solid tumor growth after a 15 day in vitro exposure of cells to either agent, after oral treatment of host animals for 20 days with either agent before injection of untreated tumor cells, and after oral treatment of host animals with either agent initiated on the day of untreated tumor cell injection. Treatment of animals with established tumors with either agent also had an inhibitory effect on tumor growth, and the effect was related to the length of treatment.Thus, exposure of these highly malignant rat prostate carcinoma cells to non‐cytotoxic doses of either agent induced slower tumor growth rates. Treatment with either agent could have selected for a slower growing population of tumor cells. Since a slowing of cell cycle transit times is an early indicator of cellular differentiation, these results could reflect an increase in the capacity of the malignant cells to differentiate.