HLA-DR-positive histiocytes in the lamina propria of the human intestine have been characterised using combined histochemical and immunohistological techniques. In the small intestine, 80-90% of the HLA-DR+ histiocytes had irregular surfaces with stellate processes, and exhibited strong membrane adenosine triphosphatase (ATPase) activity, but weak acid phosphatase (ACP) and non-specific esterase (NSE) activities (HLA-DR+ ACP+/- NSA+/- ATP++; type 1 cell). In contrast, in the lamina propria of the colon the majority (60-70%) of HLA-DR+ cells were large, round cells with strong ACP and NSE activities but no detectable ATPase activity (HLA-DR+ ACP++ NSE++ ATP+/-; type 2 cell). The colon also contained a population of type 1 cells (30-40%). In active inflammatory bowel disease affecting the colon a third population of HLA-DR+ histiocytes was seen. These cells were irregular in outline, with many processes, and were ACP++ NSE+ ATP+/- (type 3 cell). The type 3 cells appeared to replace type 2 cells. After treatment, the appearances returned to normal. These findings suggest that the different populations of HLA-DR+ histiocytes in the human intestine may have several functions, reflecting the different forms of antigen present in the intestine. The alterations in inflammatory bowel disease may represent activation in response to an invading antigen.