AbstractAnalysis of several inbred strains of rabbits with high (30–50%) frequencies of accessory spleens revealed that hereditary hematological diseases, autoimmune hemolytic anemia and lymphosarcoma, occurred in some of them. Twenty‐one per cent of individuals in these strains, though phenotypically normal, had globulin‐coated (Coombs'‐positive) erythrocytes. These findings supported observations of increased frequency of accessory spleens in human beings with similar diseases (e.g., autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, “secondary hypersplenism,” Gaucher's disease, hereditary spherocytosis, etc.) and suggested that accessory spleens represent physiological responses to demand for phagocytic capacity provided by the reticuloendothelial system in the spleen, rather than as passive developmental anomalies. This hypothesis predicted that simulation of the basic defect might yield a laboratory model for the induction and study of accessory spleens in rabbits. Phenylhydrazine was used for this purpose and it was shown that the frequency of accessory spleens in 80 rabbits so treated was 45%. Most of these accessories appeared to arise de novo because pretreatment examination in situ by laparotomy revealed a naturally occurring frequency of about 7.5%. These results supported, and provide a basis for, observations by surgeons that subsequent to an initial splenectomy, during which spleniculi were noted to be absent, recurrent indications for splenectomy would later reveal functional accessory spleens. No evidence was found to relate anemia, per se, or cardiovascular anomalies to the increased frequency of accessory spleens in rabbits. It was suggested that heritable factors limit the upward expression of accessory spleens in “normal” populations, as well as during the course of certain diseases and of phenylhydr