Superoxide anion release was studied in rat alveolar macrophages (AM), and results were compared to those obtained in other studies with polymorphonuclear leukocytes (PMN). Release of superoxide from PMN was induced by lectins (concanavalin-A (con-A)), membrane perturbants (phorbol-12-myristate-13-acetate (PMA)), and chemotactic factors (n-formyl-methionyl-leucyl-phenylalanine (FMLP)). Calcium caused superoxide release from PMN, while the sulfhydryl modifier p- chloromercuribenzene-sulfonic-acid (PCMBS), or cyclic-AMP (cAMP) decreased release. AM were obtained from male Long-Evans-hooded- rats; superoxide release was measured as reduction of cytochrome-c. Agents tested included zymosan (opsonized or unopsonized), cytochalasin-B, con-A, PMA, FMLP, n-formyl-methionyl-phenylalanine, cAMP, theophylline, two sulfhydryl group modifiers, and two amino group modifiers. Resting AM released a small amount of superoxide anion. The time course of release after zymosan stimulation was similar to that for PMN. Five to six fold stimulation was found with unopsonized zymosan. Opsonized zymosan stimulated 50 percent greater release from AM, which was much less than the effect of opsonization for PMN. The time course for AM indicated that superoxide release occurred before particle uptake. Only PMA, and to a lesser extent FMLP, increased superoxide release by resting AM, while con-A and cytochalasin-B decreased release. Theophylline and cAMP lowered resting superoxide release by AM but did not affect release in response to unopsonized zymosan. Both sulfhydryl modifiers lowered basal superoxide release, while only PCMBS affected release from zymosan stimulated AM. Calcium was necessary for superoxide release from zymosan exposed AM but did not affect basal release. The authors conclude that characteristics of superoxide release by AM and PMN show several differences with respect to activating agents and mechanisms of activation. Differences in effects of agents on basal and zymosan stimulated release by AM suggest two mechanisms for release by these cells.