Eosinophils exhibit different levels of oxidative metabolism depending on their site of origin and various host factors that may influence metabolism. The present study examined the time course of eosinophil oxidative metabolism in animals undergoing chronic peritoneal stimulation. Eosinophils were purified from the peritoneal exudates of guinea pigs stimulated with weekly polymyxin B and saline peritoneal lavage. 14C-1- and 14C-6-glucose oxidation and H2O2 production were measured at week 0 and at various time points throughout 43 weeks of stimulation. Baseline oxidative metabolism of eosinophils was relatively high throughout the time course, but then declined sharply after 32 weeks. These "deactivated" cells that were recovered after 32 weeks also failed to respond to phorbol myristate acetate (PMA) or opsonized zymosan. Electron microscopy did not reveal significant differences between deactivated eosinophils and cells from earlier time points. These findings document the time course of eosinophil activation and deactivation in this model and suggest that metabolic heterogeneity of eosinophils can occur over time in response to a chronic stimulus.