Between 1966 and 1980, 68 patients were identified who had a splenectomy before or concurrent with resection of a colorectal adenocarcinoma. Control subjects with concurrent disease were then matched with each study patient for age, sex, stage of disease, and date of operation. Follow-up was complete. Between splenectomy patients and control subjects, there was no difference in the site of primary disease (rectum versus colon), the number of patients receiving adjuvant therapy, the technique of resection (cure versus palliation), or the extent of regional disease. Overwhelming sepsis occurred in only one splenectomy patient. Splenectomy was associated with a significant decrease in survival at 5 years in patients with regional (stage C) disease but not in patients with localized (stage B) disease. More splenectomy patients received blood transfusions than control subjects, but an independent effect on survival could not be demonstrated. The mechanism responsible for this adverse impact of splenectomy is undefined. However, splenectomy should be considered a possible factor in the survival of patients operated on for regional colorectal cancer.