Numerous human macrophage (mphi) subpopulations with different behavior have been identified in adults. It is well known that peritoneal mphi are activated by abdominal surgery and subsequently contribute to a systemic inflammatory response that leads to immune suppression, increased morbidity and mortality. Information on the role of pleural mphi in adults is scarce and information on their role in children is lacking. We investigated the behavior of pleural versus peritoneal mphi in children and adolescents. As a first step, we compared the cellular composition of the pleural and peritoneal surface in children and adolescents. Pleural and peritoneal lavages were performed in 21 patients undergoing non-contaminated laparoscopic and thoracoscopic surgical procedures. We observed a significantly higher percentage of mphi in the pleural compared to the peritoneal cavity with less lymphocytes, a small amount of polymorphonuclear cells (PMNs) and other cells. To further study the mphi inflammatory response, we measured the spontaneous and LPS triggered cytokine release of isolated pleural versus peritoneal mphi (IL-1beta, IL-6, and IL-10). The pattern of cytokine release was similar in both, pleural and peritoneal mphi. Directly after lavage, they showed a strong activation, with no difference between stimulated and non-stimulated cells. After 24 h resting, mphi of both compartments reacted to LPS with a similar significant increase in the cytokine release. In conclusion, our results demonstrate that pleural mphi represent the dominant cell population in the pleural cavity of the young. They show a similar inflammatory response as peritoneal mphi and should be considered to play a major role in the local inflammatory response to thoracic surgery.