Cell cultures were established from 8 lymph nodes replaced by nodular sclerosing Hodgkin's disease. Serum-containing and serum-free conditioned media from these cultures potentiated fibroblast growth and were found to be consistently more potent than fibroblast growth factor, 100 ng/ml, every other day. Both a proliferative response and transformation-like growth were observed using BALB/c 3T3 cells, human diploid fibroblasts, and human embryonic fibroblasts as target cells. The Hodgkin's disease growth factor(s) was not produced by fibroblasts or lymphocytes in the Hodgkin's cultures and was most potent when the Hodgkin's cultures had been enriched with Hodgkin's giant cells. Removal of normal macrophages decreased the proliferative activity but did not eliminate it or nonadherent growth of 3T3 cells in agar. Control cultures of 6 nonmalignant lymph nodes, a Lennert's lymphoma, a mixed cellularity Hodgkin's disease lymph node, and a malignant histiocytosis cell line suggested that among lymph node disorders, this feature may be relatively specific for nodular sclerosing Hodgkin's disease.