Pulmonary alveolar macrophages (PAM) function as phagocytes of inhaled particulate matter and microorganisms at the air-tissue interface of lung alveoli. Changes in cellular ATP concentrations ([ATP]) and phagocytic function during acute hypoxia may be important in conditions associated with low alveolar O2. We proposed that acute hypoxia would decrease phagocytosis and reduce [ATP] in freshly isolated PAM. Phagocytic function (fluorescent microscopic technique determining percent phagocytosis in live cells) was monitored by recording uptake and retention of glutaraldehyde-fixed red blood cells (GRBC) in isolated rabbit PAM during acute incubations in air (20% O2) or hypoxia (1.7% O2). Macrophage [ATP] were determined spectrophotometrically. Acute hypoxia for 30 to 150 min decreased phagocytic function 30 to 56% in PAM without significantly affecting cell adherence and viability. Pre-exposure of PAM to hypoxia before addition of GRBC resulted in an even greater reduction in phagocytosis (97% decrease by 30 min), and recovery of phagocytic function occurred 60 to 90 min after returning PAM to air. The cellular retention of phagocytosed GRBC (percentage of PAM with GRBC and number of GRBC/PAM) was reduced 30% by 1 h of hypoxia. Compared with [ATP] of PAM in air, [ATP] of PAM exposed to hypoxia were reduced 55 and 35% at 30 and 60 min, respectively. Compared with [ATP] of cells with GRBC in air at 0 and 30 min, PAM with GRBC in hypoxia for 30 min had, respectively, 61 and 40% lower [ATP]. By 60 min with GRBC, PAM [ATP] in air and hypoxia were similar but were 50% lower than [ATP] at time 0.(ABSTRACT TRUNCATED AT 250 WORDS)