The usual methods for the functional evaluation of the spleen in man are based on the measurement of a) spleen volume, b) spleen uptake of particles from the circulating blood, and c) morphological abnormalities of circulating erythrocytes. Analysis of clearance curves of damaged autologous erythrocytes, measurement of spleen size or volume by scintillation scanning and counting of erythrocytes with pits by interference contrast microscopy at present are the most widely used techniques. The most frequent causes of acquired functional abnormalities of the spleen are the sickle cell diseases, inflammatory intestinal diseases, immune complex diseases, chronic myelogenous leukemia, irradiation, hemophilia, and the hyposplenism of newborn infants and of the elderly. Usually there is a parallelism enlarged or normal-sized spleen with decreased function, has been observed in sickle cell syndromes and occasionally in chronic myelogenous leukemia and hemophilia.