COPD is associated with defective efferocytosis (apoptosis and alveolar macrophage (AM) phagocytic function) that may lead to secondary necrosis and tissue damage. We investigated ex vivo AM phagocytic ability and recognition molecules (CD36, integrin V3, CD31, CD91, CD44) using flow cytometry. The transferrin receptor [CD71] was measured as an indicator of monocyte-macrophage differentiation in BAL. Proliferation was assessed with Ki-67. Based on evidence of systemic involvement in COPD, blood from 17 current-smoker and 25 ex-smoker COPD subjects, 22 healthy smokers, and 20 never-smoking controls were also investigated. BAL was collected from 10-16 subjects in each group. Levels of recognition molecules and cAMP were assessed following exposure of AM to cigarette smoke in vitro. The phagocytic ability of AM was significantly decreased in both COPD groups and healthy smokers compared to controls. However, phagocytic capacity was better in COPD subjects who had ceased smoking, compared to those who were still smoking. AM from current-smoker COPD subjects and healthy smokers exhibited reduced CD31, CD91, CD44 and CD71, and enhanced Ki-67 compared to healthy never-smoker controls. There were no differences in these markers in AM from ex-smoker COPD subjects compared to controls, or in blood monocytes from any group. Suppressive effects of cigarette smoke on AM recognition molecules associated with an increase in cAMP were confirmed in vitro. Our data indicates that a smoking-related reduction in AM phagocytic ability and expression of several important recognition molecules may be at least partially normalised in those COPD subjects who have ceased smoking.