A clonal lymphoblastoid cell line derived from lymph node of a patient with Hodgkin's diseasewas cultivated in diffusion chambers implanted in the abdominal cavity of mice and cellular morphologic changes were sequentially studied for up to 8 weeks. The majority of cells before intraperitoneal implantation were lymphoblasts with approximately 16% mature lymphocytes. However, after 3 weeks of in vivo cultivation in diffusion chambers, macrophage-like cells began to increase and occupied 80-90% of cells after 4 and 5 weeks. These macrophage-like cells, when tested for phagocytic activity after 4 weeks, exhibited bacterial phagocytosis. Labeling studies with (3)H-thymidine indicated that active DNA synthesis continued for up to 2 weeks of in vivo diffusion chamber cultivation, during which mitotic figures were also observed morphologically. Further, it was attempted to recultivate in vitro cells that were taken out of diffusion chambers after 2, 3, and 4 weeks of in vivo implantation. These 3 separate attempts led to the development of lymphoblastoid cells that were morphologically and cytogenetically similar to those prior to diffusion chamber implantation. From these findings, it is suggested that human lymphoid cells undergo morphologic alteration to macrophages under certain circumstances.