Superoxide anion (O2-) release by monocytes from leprosy patients in a paired study was lower than that released by monocytes from healthy controls. Pretreatment of healthy control monocytes with phenolic glycolipid-I (PGL-I) of Mycobacterium leprae resulted in the release of less O2- than released by buffer-treated cells or cells pretreated with structurally similar lipids. However, pretreatment of patient monocytes with PGL-I did not affect the O2- generation, perhaps because the cells already had a lower capacity to produce O2-. Upon further examination of the data from the patient population, monocytes from lepromatous patients released significantly less O2- than cells from normal controls, while tuberculoid patient cells released O2- in amounts similar to that generated by cells from normal controls. In addition, monocytes from patients with a high bacterial index had a lower capacity to generate O2- when compared to cells from healthy individuals.