Relationship of the spleen to the cellular elements of the blood, and subsequent finding of a leukopenic substance in inflammatory tissue.

1. The effects of splenectomy on the cellular elements of the circulating blood in the male albino rat have been investigated. Only a quantitative change in the leukocytes was observed. This change was in the form of a marked leukocytosis. The leukocytosis reached a peak 8 to 10 days after splenectomy and was maintained for a period of several months at a significantly higher liver than that which was observed to follow other comparable operative procedures. 2. Subcutaneous injection of acetone desiccated splenic powder caused a leukopenic reaction in 17 hours in splenectomized rats, but the leukopenia was found not to be related specifically to the spleen. 3. Subcutaneous injection of insoluble tissue powders caused inflammation at the site of injection. A saline extract of the excised inflammatory tissue produced a profound leukopenia in 4 hours following subcutaneous injection. The leukopenia lasted 4 to 6 hours and was due to a reduction in both polymorph nuclear and mononuclear cells. 4. The leukopenia-producing substance in the saline extract of inflammatory tissue was called the leukopenia-depressing factor or L.D.F. 5. The L.D.F. was found to be heat stable, not coagulable by heat, non-dialyzable, and stable in saline at 5°C. for a period of several months. 6. Ultracentrifuge analysis of the lyophilized powder suggested that the soluble sedimenting components are of small molecular weight, presumably between 10,000 and 20,000. Electrophoretic analysis showed there to be at least five components. A positive Molisch test demonstrated the presence of carbohydrate material. Chemical analysis showed that it contained 0.13 per cent phosphorus and 13.26 per cent nitrogen. 7. The L.D.F. in the saline extract of inflammatory tissue is compared with five other similar leukopenia-producing substances reported in literature.