No definite statement can as yet be made as to the places of formation of the non-granulated large mononuclear leucocytes.
Kurloff has demonstrated, that in the guinea-pig these cells are present both in the bone-marrow and in the spleen, but that after extirpation of the spleen the absolute number does not change. The bone-marrow then in the guinea-pig can also preserve the balance of the large mononuclear, non-granular cells in the blood.
The numbers we found in our blood investigations in man after splenectomy were also normal. We may then doubtless assume that the large mononuclear granuleless cells of human blood also arise for the most part from the bone-marrow. In this tissue they are to be picked out in the medley of the different kinds of cells only with the utmost difficulty, owing to their small number and their but little characteristic properties. Consequently an exact investigation of their origin could probably only be successful if it were possible experimentally to produce a disease in which these forms in particular underwent important increase. This advance is not quite hopeless, since in man at least an absolute increase of the large mononuclear cells is observed in the post-febrile stage of measles.
On the grounds merely of microscopical investigations we conclude that the bone-marrow is by far the most important of the blood-forming organs, for its function is the exclusive production of red blood discs as well as of the chief group of the white corpuscles, the polynuclear neutrophil.
=The physiological, experimental investigation= of the functions of the bone-marrow offers insurmountable difficulties. An exclusion of the whole bone-marrow or of larger portions only is an impossible operation. Nor can we ascribe any value to the researches which endeavour to obtain a result by comparative enumerations of the arterial and venous blood of a bone-marrow area. J. P. Roietzky working under Uskoff's direction has recently made counts of this kind in the dog, from the nutrient artery of the tibia and the corresponding vein. He found that the number of white corpuscles of the vein is slightly greater, that on the other hand the absolute number of "young corpuscles" (Uskoff), _i.e._ of the lymphocytes, has been considerably diminished, whilst the number of "ripe" corpuscles, which for the most part correspond to our polynuclear, is considerably increased. He gives the following table: