The influence of LPS on peritoneal and spleen cell oxidative metabolism was investigated in LPS sensitive (C57BL/6) and LPS resistant (C3H/HeJ) mice following intraperitoneal or subcutaneous injection, by measurement of chemiluminescent (CL) responses to latex particles. In C57BL/6 mice, LPS induced a marked increase in peritoneal and spleen cell CL responses, regardless of the route of injection. On the 2nd day, the effect of LPS on peritoneal cells could be fully explained by an inflammatory reaction, while on the 4th day it could be related to an "activated state" of peritoneal macrophages. In contrast, such an in vivo effect of LPS in peritoneal or spleen cell CL responses was not found in C3H/HeJ mice except on the 2nd day following the injection and with the highest LPS dosage and could be totally due to the LPS induced inflammatory reaction. In vitro studies showed that extremely low concentration of LPS increased CL response capacities of C57BL/6 spleen cell to latex particles. In contrast, CL responses from C3H/HeJ spleen cells remained unaffected by LPS except when submitted to concentrations which proved toxic for the sensitive strain CL producing cells. These results lend additional evidence for the involvement of reactive oxygen species (ROS) in the metabolic consequences of LPS-induced macrophage activation.