Resident peritoneal macrophages from New Zealand Black (NZB) mice release O2- and H2O2 after adherence to a plastic surface without any chemical or particulate stimulant. This phenomenon is age dependent and more pronounced in animals with sever autoimmune disease. Significant differences were observed between the high and low breakage NZB sublines (HB and LB), which were previously developed by selective matings on the basis of chromosome breakage rates. The LB subline differs significantly from the HB subline with respect to autoimmune hemolytic anemia and tumor incidence. When the macrophages were stimulated with the tumor promoter TPA, the number of "responders" was higher in the HB than in the LB subline and correlated with the degree of splenomegaly, that is, with the severity of the disease. A negative response to agonist stimulation and very low spontaneous production of active oxygen species was observed in NZW and Swiss mice, which is the normal finding for resident macrophages according to data from the literature. The increased superoxide and hydrogen peroxide production by macrophages of NZB mice is discussed with respect to autoimmune disease and cancer.