We studied the effect of cyclophosphamide on survival of mice and the incidence of tumor implants in various organs following both i.v. and intraarterial dissemination of tumor cells. Female C3H/HeN mice received cyclophosphamide (240 mg/kg) i.p. 4 days prior to inoculation of various doses of KHT tumor cells. Mice were followed to death, and the amount of tumor present was roughly quantified. Following i.v. inoculation of tumor cells, survival was decreased in cyclophosphamide-treated mice compared to control mice. However, survival was not affected by treatment with cyclophosphamide in mice receiving intracardial tumor cell injections. Pretreatment with cyclophosphamide caused a dramatic increase in the number of lung tumor implants following both routes of tumor cell administration. A similar tumor-promoting effect by cyclophosphamide could not be documented in the brain, heart, kidney, adrenal, or ovary. The study suggests that cyclophosphamide has a much greater effect on ultimate deposition and growth of tumor implants in the lungs than in other systemic organs or in the central nervous system.