Tumor nodules from spleens removed at staging laparotomy for nodular sclerosing Hodgkin's disease were grown as fragment cultures in vitro. These cultures could be maintained in vitro for up to 2 months and consisted of 90% large, adherent multinuclear and mononuclear cells. Immunologic markers and enzyme histochemistry suggested that the cultured cells belonged to the monocyte/macrophage lineage. Supernatants from these cell cultures were then assayed for the monokine Interleukin I and for fibroblast stimulatory factors, which were both present. These results are discussed in considering Hodgkin's disease as a neoplasm of the monocyte/macrophage lineage, capable of producing functionally active mediators that may account for the histopathologic appearance observed.