SEVERAL permanent murine macrophage-like cell lines exhibiting various macrophage-associated effector functions have been described^1–3, but establishment of permanent human macrophage cell lines has been much more difficult⁴. Recently Sundström and Nilsson⁵ reported the establishment of a human histiocytic lymphoma cell line, U937, with macrophage characteristics. This line was further adapted to rapid growth in vitro by Lachman et al.⁶. During studies of major histocompatibility complex antigens on a number of human lymphoid cell lines we failed to detect Ia-like antigens (HLA-DR) on U937. Because these alloantigens have been reported to occur on early myeloid cells⁷ and might therefore be regarded as differentiation antigens of stem cells, an attempt was made to produce differentiation and expression of new cell surface molecules on U937. Procedures similar to those used to produce differentiation of myeloid cell lines⁸ and promote growth of macrophages in culture were tried. Although U937 cells failed to express Ia-like antigens they underwent remarkable morphological and functional changes. We report here that U937 can be activated by supernatants from human mixed lymphocyte cultures (MLC). Although this activation takes several forms, the findings reported here show marked augmentation of antibody-dependent cellular cytotoxicity (ADCC) against erythroid and tumour target cells.