Eighteen spleens derived from patients with hairy cell leukemia (HCL) were analyzed by correlative scanning and transmission electron microscopy. In 15 of the cases, the white pulp areas were markedly decreased or absent when compared to normal spleens, although few hairy cells were observed within this region. In only one case did the white pulp appear normal. In all HCL cases, hairy cells were observed within normal, dilated, and abnormal sinuses. The abnormal sinuses contained hairy cells of typical morphology attached to other hairy cells, to endothelial lining, and to erythrocytes. The degree of sinus filling by hairy cells varied from loosely- to tightly-packed. Endothelial cells exhibiting degenerative changes, such as swelling with smooth surfaces and dilated intercellular spaces, were frequently seen. These results indicate that in addition to the previously described overcrowding of the spleen by hairy cells, the splenic tissue itself is considerably altered and sometimes severely damaged in patients with HCL.