The present study is an attempt to verify the hypothesis that high (HI) and low (LI) antibody responder Biozzi mice, which differ strikingly in their macrophage capacities to catabolize antigens and to exert bactericidal activity (the LI being more potent than the HI line), demonstrate a similar genetic disparity in their macrophage oxidative metabolism activation potential. The production of reactive oxygen intermediates was measured by luminol-dependent chemiluminescence in cell suspensions from various sources including: bone marrow, peripheral blood, spleen, peritoneal exudate, thymus, and mesenteric lymph nodes. Chemiluminescence was determined both in the absence and presence of particulate (opsonized zymosan and latex) and soluble (phorbol myristate acetate and concanavalin A) membrane-stimulating agents. Lastly this investigation was conducted both in normal and endotoxin (lipopolysaccharide from Escherichia coli) treated HI and LI mice in an attempt to unmask the hypothesized difference by increasing the macrophage oxidative response capacity. Results obtained did not show the expected interline differences in reactive oxygen intermediate production regardless of cell origin, stimulating agent or lipopolysaccharide in vivo treatment. On the other hand, the well-documented enhancing effect of lipopolysaccharide on macrophage oxidative metabolism depended on the origin of the cell suspension. Indeed, it was not observed in bone marrow and peripheral blood from either HI or LI mice, was clearly demonstrated in the spleen and peritoneal exudate from both mouse lines, and surprisingly, in the thymus and lymph nodes from HI but not LI mice.