Information was sought on the antigen-presenting cells (APC) required for stimulating primary mixed-lymphocyte reactions (MLR) by unprimed Lyt-2+ cells in the absence of added lymphokines. Like L3T4+ cells, Lyt-2+ cells gave very high MLR in response to H-2-different dendritic cells (DC). Surprisingly, high MLR were also elicited by thioglycollate-induced peritoneal exudate cells (PEC), including Ia- PEC; these cells were non-immunogenic for L3T4+ cells. Since PEC consisted almost entirely of macrophages (M phi), the data suggest that at least two different cell types, DC and M phi, can express APC function for unprimed Lyt-2+ cells. Since resident peritoneal M phi and in vitro cultured PEC were poorly immunogenic, the APC function of M phi might be limited to a subset of these cells, e.g. to immature M phi.