Abstract: The effects of six naphthalenesulfonamide derivatives were studied on the LPS-induced release of tumor necrosis factor (TNF) from mouse peritoneal macrophages primed with A₂₃₁₈₇. The calmodulin (CAM) antagonist, N-( 6- aminohexyl )- 5- chloro- 1- naphthalenesulfonamide (W-7) and its derivatives N-( 6- aminobutyl )- 5- chloro- 1- naphthalenesulfonamide and N- ( 6-aminoethyl)-5-chloro-1-naphthalenesulfonamide (10～400 ng/ml) were found to inhibit LPS-induced TNF release in a dose-dependent manner, and the protein kinase C (PKC) activator, N-(n-heptyl)-5-chloro-1-naphthalenesulfonamide (SC- 10) and its two derivatives, N- ( n- quinyl )- 5-chloro-1-naphthalenesulfonamide and N-(n-butyl )- 5- chloro-1- naphthalenesulfonamide ( 1～16μg/ml) were shown to increase LPS-induced TNF release at suboptimal doses in a dose-dependent manner. These results suggest that the LPS-induced release of TNF is CAM-dependent and PKC may play an important role in this process.