We measured H202 release by human alveolar macrophages (AM) from normals and sarcoid patients in suspension immediately after bronchoalveolar lavage in the presence and absence of the triggering agent, phorbol myristate acetate (PMA). AM from 11 sarcoid patients produced a mean (±SE) of 21.7±23 and 5.9±3.4 umol H202/10' macrophages in the presence and absence of PMA, respectively. By contrast, AM from normals (n = 6) produced 9.8±1.7 and 1.6±0.7 nmol H202/106 macrophages with and without PNMA, respectively. Macrophage activation, as monitored by H202 production, did not correlate with the angiotensin-converting enzyme levels, the result of gallium-67 scans, or the percent of lymphocytes in the bronchoalveolar lavage. To determine whether AM from normals could be stimulated to increase their H202 production to the level seen in patients with sarcoid, we measured H202 released by adherent AM after incubation in each of four potential activating agents: recombinant interferons aA, B, -y (rIFNaA, rIFN,6, and rIFN'y, respectively), and 1,25-dihydroxyvitamin D3. H202 release in the range seen in sarcoid patients could be induced in PMAtriggered AM from normals by rIFN-y in a time (t½ -1 d) and dose-dependent fashion (threefold increase, ECso 5 antiviral U/ ml) and by rIFNaA and rIFN# at higher concentrations, but not by 1,25-dihydroxyvitamin D3.