During an acute nonspecific inflammatory reaction initiated in the pleural cavity by a nondiffusible stimulus (calcium pyrophosphate crystals), the oxidative metabolism, as measured by chemiluminescence and superoxide release, of cells harvested from both the inflammatory site and at points distant from it was studied.The oxidative metabolism of peritoneal macrophages, obtained from rats undergoing an inflammatory reaction (pleurisy), demonstrated a transient decrease in activity compared with the resident population when using both zymosan and phorbol myristate acetate as stimulants. This metabolic unresponsiveness induced by inflammation may be related to the concomitant changes in the levels of prostacyclin in the peritoneal cavity. It should be emphasized that the peritoneal cellular composition or number did not change during these events. On the other hand alveolar macrophages from inflamed animals showed no significant changes in their superoxide production or chemiluminescence compared to controls. The precise reason for these inflammation‐induced changes is unknown; however the acute nonspecific inflammatory reaction was able to modulate the oxidative metabolism of cells not only at the site of inflammation, but at points distant from it.