Phagocytosis in alveolar macrophages (AM) was enhanced in rats starved for 2-3 days, and was suppressed by over 4 days of starvation. We investigated the mechanism of this phenomenon. AM from starved rats were separated into four subpopulations, designated I, II, III, and IV, using discontinuous Percoll gradient centrifugation. Phagocytosis was more active in the higher-density fractions (III and IV) than in the lower-density ones (I and II). At 2 days of starvation, the phagocytic activity of the higher-density fractions was higher than that of the same fractions from fed rats. Pulmonary surfactant isolated from rat lung bronchoalveolar lavage fluid had a higher content of surfactant apoprotein A (SP-A) in samples from rats starved for 2 days compared with fed controls, but the level returned to the baseline by 4 days of starvation. Phagocytosis by AM was enhanced dose-dependently by SP-A, and the effect was completely inhibited by an antibody against SP-A. AM subpopulations exposed to SP-A showed enhanced phagocytic activity in the higher-density fractions (III and IV), whereas little change was evident in the lower-density fractions (I and II). These results support the concept that pulmonary surfactant and its apoprotein, SP-A, are factors that regulate the lung defense system including activation of AM, and are effected by starvation.