The influence of a functional spleen on induction and growth of cancer is unknown. Both beneficial and detrimental results have been observed in tumor-bearing hosts following splenectomy. We examined the effect of splenectomy, splenic autotransplantation, and splenic preservation on the induction and growth of 1,2-dimethylhydrazine (DMH)-induced murine colon cancer. Following splenectomy there was a significant increase in malignant tumors but no increase in benign tumors. To rule out the possibility that splenectomy increased the carcinogenicity of DMH by decreasing the capacity for DNA repair in colon cells, the units of 06-alkylguanine DNA alkyltransferase were measured in tumor-free and malignant colon tissue from both splenectomized and control rats. This repair protein was chosen because it is known to protect cells from the mutagenic effects of methylating agents. There was no significant difference in the alkyltransferase activity of tumor-free colon vs malignant tumor or between treatment regimens. Thus, the ability of the spleen to protect rats from the induction of malignant colon tumors induced by DMH is most likely due to preservation of immunologic surveillance in the host.