Sarcoid granulomata result from aberrant immunological reactions initiated by antigen--presenting macrophage--like cells, and maintained by other effector macrophages. These macrophages can be distinguished phenotypically by monoclonal antibodies RFD1 and RFD7 (which recognize dendritic cells and mature macrophages respectively). Active sarcoid BAL contains a high proportion of RFD1 + cells (mean 44.7% compared to 12% in normals). Much of this increase is accounted for by the emergence of macrophages with the double phenotype RFD1 + D7 + (27.2% compared to 7% in normals), the proportion of which increases with disease severity and returns to normal in remission. When isolated from BAL by using plastic plate adherence and metrizamide density gradient, this hitherto unknown RFD1 + D7 + subset displays distinctive phenotypic, physiological and functional features. Unlike RFD1 + D7-cells, RFD1 + D7 + macrophages adhere to plastic, are acid phosphatase positive with increased phagocytosis, have marked Fc and c3b receptor expression, and suppress T-lymphocyte reactivity. In active sarcoidosis, this suppressive action is accentuated, and a greater proportion of RFD1 + D7 + cells express Fc receptors as well as a separate antigen RFD9 (which identifies epithelioid cells). Furthermore we have observed that gamma-interferon, produced in high concentration by activated T-lymphocytes induces not only HLA-DR molecules on cells, but has also been shown in vitro to increase the proportion of RFD1 + cells developing while suppressing RFD7 expression. It therefore seems that the increased proportion of RFD1 + D7 + macrophages seen in active sarcoidosis could arise as a result of an increased induction of RFD1 expression on macrophages which express RFD7.(ABSTRACT TRUNCATED AT 250 WORDS)