Infections are frequent complications in end-stage renal failure patients undergoing hemodialysis (HD), and peripheral blood monocytes are important cells in host defense against infections. The majority of circulating monocytes express high levels of lipopolysaccharide receptor antigen CD14 and are negative for the immunoglobulin Fcγ receptor type III (CD16). We studied the occurrence of a minor subpopulation coexpressing low levels of CD14 together with CD16 in HD patients. In healthy controls CD14+ CD16+ monocytes account for 8% ± 4% of CD14+ monocytes, with an absolute number of 29 ± 14 cells/μl. In stable HD patients the CD14+ CD16+ subpopulation was significantly elevated (14% ± 3%, or 66 ± 28 cells/μl), while the number of CD14++ monocytes (monocytes strongly positive for CD14) remained constant. In HD patients suffering from chronic infections a further rise in CD14+ CD16+ monocytes was observed (128 ± 71 cells/μl; P < 0.01) such that this subpopulation constituted 24% of all blood monocytes. In contrast, numbers of CD14++ cells did not change compared to those for stable HD patients, indicating that the CD14+ CD16+ monocyte subpopulation was selectively expanded. During acute infections the CD14+ CD16+ cell subpopulation always expanded. A whole-blood assay revealed that CD14+ CD16+ monocytes exhibited a higher phagocytosis rate for Escherichia coli bacteria than CD14++ monocytes, underlining their role during host defense. In addition, CD14+ CD16+ monocytes expressed higher levels of major histocompatibility complex (MHC) class II antigens (HLA-DR, -DP, and -DQ) and equal amounts of MHC class I antigens (HLA-ABC). Thus, CD14+ CD16+ cells constitute a potent phagocytosing and antigen-presenting monocyte subpopulation, which is expanded during acute and chronic infections commonly observed in chronic HD patients.