The dose response to 3-methylcholanthrene (3-MC), the promoter effects of 2,6,IO, I 4-tetramethylpentadecane (pristane) and the target-organ specificity in the preferential induction of 6-lymphoid malignancies versus thymic tumors were examined. Lymphoid malignancies were induced in approximately 30% of the Copenhagen rats treated with injections in Peyer's patches (PP) of low, intermediate or high doses of 3-MC. A low dose of 3-MC induced B-lymphocytic leukemias or B lymphomas, whereas thymic tumors were detected in rats treated with high doses. Co-treatment of rats with pristane and 3.MC resulted in increased incidences and decreased latency of the lymphoid malignancies observed, suggesting that pristane acts as a tumor promoter. To address the possible role of PP in the induction events, PP were surgically removed after 3-MC treatment and the remaining small intestine anastomosed. Thymic tumors, but no Blymphoid malignancies, were observed, indicating that the PP environment was important in the induction of the 8lymphoid malignancies. Radiotracer studies also revealed that appreciable amounts of 3-MC were disseminated to the thymus within 24 hr after treatment of PP with a high dose of 3-MC. Furthermore, direct intr'athymic injection of the thymus with 3-MC resulted in the development of thymic tumors only. These results support the hypothesis that the PP has an important role in early events in the carcinogenesis of B lymphocytes and in the dissemination of 3-MC to the thymus.