In order to clarify the role of monocytes and macrophages in the formation of sarcoid granulomas, primary cultures of sarcoid tissues were initiated with biopsied specimens from patients with sarcoidosis (6 lymph nodes and one subcutaneous nodule), and compared with primary cultures of 5 lymph nodes obtained from patients with other disorders. The number of monocytes and macrophages migrating from tissue explants was larger in sarcoid tissues than in non-sarcoid tissues. In the cultures of sarcoid tissues, the monocytes and macrophages aggregated at the second week of cultures and multinucleated giant cells were observed at the third week. However, these findings were not observed in the culture of non-sarcoid tissues. At the fourth week, the aggregated macrophages and multinucleated giant cells disappeared and fibroblasts developed. The lysozyme activity of the culture medium of sarcoid tissues was higher than that of non-sarcoid tissues, but no difference was observed in angiotensin-converting enzyme activity. These results suggest that the monocytes and macrophages in sarcoid granulomas have been activated by unknown factors and may transform to epithelioid cells constituting sarcoid granulomas.