The rat antihuman lymphocyte monoclonal antibodies CAMPATH-1M and CAMPATH-1G (IgM kappa and IgG2b kappa, respectively) recognize cell surface antigens (CDW52) present on normal T and B lymphocytes as well as on monocytes, with weak expression on neutrophils. In previous studies, when peripheral blood mononuclear cells were treated with CAMPATH-1M and human complement, more than 99% of lymphocytes were killed. The present study indicates that both CAMPATH-1M and -1G bind to peripheral blood neutrophils and monocytes and do not affect the activity of the former cells but decrease the functional activity of monocytes. Decreased functional activity includes suppressed superoxide production by monocytes in response to phorbol myristate acetate (PMA), reduced activation of the cells as indicated by decreased ability to reduce 3-(4.5-dimethylthiazol-2-yl)-2.5 diphenyl-tetrazolium bromide (MTT), reduced tumoricidal activity, and reduced capability to kill Candida albicans. The ability of CAMPATH-1 to suppress the functional activity of monocytes in vitro suggests that in vivo administration of CAMPATH-1G may also affect the function of monocytes.