We have previously observed that while several cytokines were able to modulate histocompatibility antigens, that not all cytokines were similar in the pattern of augmenting histocompatibility antigen expression. Whereas IL-4, GM-CSF and IFN-gamma all enhanced the expression of HLA-DR and HLA-DP antigens on monocytes, only IFN-gamma augmented the expression of HLA-DQ. While IFN-gamma and IFN-alpha augmented class I (HLA-A,B,C antigens) on monocytes, IL-4 and GM-CSF did not. These studies were extended to look at other cell lines. THP-1 is a human monocyte-like cell line. Although this cell has receptors for IL-4, like monocytes, it did not respond to IL-4 or GM-CSF in the augmentation of HLA-DR antigen expression. The THP-1 cell line responds dramatically to IFN-gamma. Differentiating agents, such as DMSO, PMA, retinoic acid, did not alter the response of THP-1 cells to IL-4 or GM-CSF. Two other non- myeloid cell lines were also examined. Normal human endothelial cells, and a human adenocarcinoma cell line, had increased expression of HLA-DR antigens after treatment with IFN-gamma, but not after treatment with either IL-4 or GM-CSF. These studies will help us understand not only histocompatibility antigen expression, but cytokine function as well.