To determine the causes and time course of onset of functional asplenia in adults, a four-part investigation was conducted. This consisted of a review of the world's literature, a survey of colleagues, a detailed study of 4,476 consecutive liver-spleen scans in three hospitals, and continued monitoring of 3,500 scans in five hospitals. Based on the findings, a classification was proposed of the causes of functional asplenia. The two major etiologies were circulatory disturbances and effects directly on splenic reticuloendothelial cells. The time course varied from the essentially instantaneous onset of functional asplenia in patients with acute splenic artery obstruction, to a prolonged and gradual onset in those with chronic damage to splenic reticuloendothelial cells. Functional asplenia was found in 0.14% of the adults who had liver-spleen scans for other indications.