Antigen-pulsed neutrophils from mouse peritoneal cavities displayed a remarkable level of lymphocyte proliferative activities to antigen-primed T lymphocytes. Genetic mapping studies demonstrated that compatibility at the IA, as well as IE/C, subregions of the major histocompatibility complex (MHC) was essential for effective presentation of the lysozyme antigen. These antigen-presenting activities were remarkably inhibited by anti-Ia sera. Inhibition tests revealed that neutrophil immune-associated (Ia) antigens seem to be essential for antigen presentation during the initial 8 hr. Elimination studies of antigen-pulsed neutrophils with alloantisera plus complement revealed these antigen-presenting neutrophils bearing both IA and IE/C gene products on the same cells. These results suggest that Ia-positive neutrophils might play a role in the immune response through antigen presentation.