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Proliferation and differentiation of granulocyte and macrophages in the bone marrow i regulated by glycoproteins called Colony - Stimulating - Factors (CSF). Lung is a very active tissue in the production of this protein. Although the characteristics of CSF have been studied extensively, the mechanism of its production is still unknown. In this study the - effect of Indomethacin on the CSF production has been investigated. Addition of different concentrations of Indomethcin to the lung conditioned medium and measuring the CSF - activity on bone marrow stem cells in semi - solid agar cultures shows that Indomethacin at 1µg/ml enhances CSF production, but at higher concentrations inhibits it. Using exogenous Prostaglandins El and E2 in the presence and absence of Indomethacin reverses enhancing effect, however, they have no significant effect on normal CSF production by the lung. Removal of alveolar macrophages by lavaging also diminished Indomethacin effect to 50% but not to normal level. From the results obtained above, it is concluded that Indomethacin enhances CSF production by the lung tissue. Prostaglandins and macrophages, although affect this, process but have not a significant role on the normal CSF production. Therefore the role of other cellular types of the lung should be considered in this mechanism.