=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: ------------------------------------------------------------- Total number | Young | Ripe | Old | corpuscles | corpuscles | corpuscles ------------------------------------------------------------- Arterial blood 15000| 1950 (13%) | 840 (5.6%) | 12210 (81%) Venous " 16400| 656 (4.0%)| 2788 (17.0%)| 12956 (79.0%) The argument based on figures such as these assumes that the function of the bone-marrow is =continuous=; an assumption which Uskoff indeed seems to make. But if the bone-marrow is constantly absorbing the lymphocytes to such an extent, it is quite incomprehensible how the normal condition of the blood can be preserved, bearing in mind the extent of the bone-marrow and the rate of the circulation. All evidence indeed tends to shew that on the contrary the bone-marrow performs its functions discontinuously, inasmuch as elements continually grow to maturity in the bone-marrow, as we have above explained, but they only emigrate at certain times as the result of chemical stimuli. It is obvious _a priori_ from this consideration how inconclusive must be the results of experiments such as these of Roietzky[17]. Far more important for the elucidation of the function of the bone-marrow are =clinical observations= on cases in which considerable portions of the bone-marrow are replaced by tissue of another kind. We may best divide the observations on this point into two groups: 1. malignant tumours of the bone-marrow, 2. the so-called acute leukaemia. There are unfortunately very few available observations as yet upon the first group. Still rarer are the cases in which as is necessary the whole bone-marrow has been subjected to an exhaustive examination, which alone affords adequate evidence of the extent of the defect.