The capacity of alveolar macrophages from mice injected with a metastatic Lewis lung carcinoma variant, LLC-C3, to regulate T-cell Con A blastogenesis and NK cytotoxicity was studied. During the first 5 days after subcutaneous tumor injection, alveolar macrophages were stimulatory to Con A blastogenesis of normal spleen cells. After 5 days, the alveolar macrophages shifted to become suppressive. The suppressive activity was extensive by day 11, when the primary and metastatic tumor foci were first detectable. The tumor-bearer alveolar macrophages also suppressed NK cytotoxicity. Alveolar macrophage suppressive activity was sensitive to indomethacin, suggesting a prostaglandin-dependent suppressor mechanism. Suppression was not mediated by the production of hydrogen peroxide or superoxide, as it was insensitive to catalase or superoxide dismutase. When normal alveolar macrophages were cultured with LLC-C3 supernatants for over 12 hours, suppressive activity was induced. The results of these studies show that alveolar macrophages of tumor bearers become suppressive with progressive tumor growth and might, thus, facilitate the development of pulmonary metastases.