Parapneumonic pleural effusions are associated with the presence of a variety of inflammatory cells whose influx into the pleural space is attributed to the presence of inflammatory cytokines. Macrophage inflammatory protein-1α (MIP-1α), an important mononuclear chemokine, plays a critical role in pulmonary parenchymal inflammatory disease, but its role in the recruitment and activation of mononuclear phagocytes in the pleural space is unknown. In this study we demonstrate that complicated parapneumonic pleural effusions (empyema) and uncomplicated parapneumonic pleural effusions contain significantly (P < .001) higher levels of MIP-1α with higher numbers of mononuclear cells when compared with effusions resulting from malignancy and congestive heart failure. The MIP-1α was biologically active and contributed 43% and 37% of the mononuclear chemotactic activity of complicated and uncomplicated parapneumonic pleural fluids, respectively. In vitro, human mesothelial cells, when stimulated with interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), or bacterial lipopolysaccharide (LPS), produced MIP-1α. Northern blot analysis confirmed that both endogenous (IL-1β or TNF-α) and exogenous (LPS) factors induce MIP-1α expression in mesothelial cells. Supernatants from activated mesothelial cells demonstrated chemotactic activity for mononuclear cells. This activity was blocked by MIP-1α antibody, indicating that the MIP-1α released was biologically active. We conclude that in parapneumonic pleural effusions, MIP-1α plays a major but not exclusive role in the recruitment of mononuclear leukocytes from the vascular compartment to the pleural space, and pleural mesothelial cells by production of MIP-1α actively participate in this process.