The “pit count” or pocked erythrocyte (Pk RBC) count (PC) is the percentage of RBCs containing one or more vesicles visualized by phase interference microscopy. The PC is <1.5% in normal subjects and 25-60% in surgically splenectomized patients; values between these extremes may result from splenic hypofunction. Although the PC is being increasingly utilized as a test of splenic function, little information is available about the patterns of formation and removal of these organelles. We performed serial PCs following splenectomy (S) in 4 patients. Levels began to rise within 1 week and reached a plateau (30-50%) by 6 to 8 weeks. Similar results were obtained following S of dogs, except that the steady state plateau value was only 10-13%. Rats initially exhibited a similar pattern of rise in PC post-S, but from the 4th to 10th week the PC gradually declined to 3%; splenosis or accessory spleens were not visualized at autopsy. Rabbits had only a slight and inconsistent rise in PC after S. Rate of removal from the circulation of Pk RBCs was determined by exchange transfusion of blood from a splenectomized dog into a eusplenic animal. Clearance of the Pk RBCs was linear, with a t1/2 of 8 hours. We conclude that Pk RBCs rise slowly following S, rapidly disappear from the circulation in the presence of a normal spleen, and vary in the pattern of rise and peak levels following S among different animals.