This study was designed to examine the inflammatory response in rabbits to intradermal injections of lymphokine-containing supernatants from cultured cutaneous sarcoidal granulomas (sarcoidal supernatant). Cell-free sarcoidal supernatants and concurrently incubated culture medium controls, alone or mixed with heat-inactivated K-S antigen or BLB, were injected intradermally into rabbits. These were, compared to control results, increased inflammatory reactions with histiocytes and epithelioid cells at the injection sites in 9 out of 11 experiments using sarcoidal supernatants mixed with K-S antigen and in 8 out of 10 experiments with these supernatants mixed with BLB. Sarcoidal supernatant alone, control medium, or normal saline solution produced no inflammatory response. Supernatants from cultured normal skin tissues obtained from sarcoid patients and those obtained from surgical patients free of sarcoidosis, when mixed with K-S antigen or BLB, showed variable inflammatory responses similar to the response seen with sarcoidal supernatants, but these were not significantly different from those of their own controls. It was concluded that lymphokines released locally may initiate and maintain the formation of sarcoidal granulomata.