Background: We aimed to investigate the immunosuppressive effects of several calcium channel blockers as potential new anti-inflammatory drugs. We examined whether calcium channel blockers can inhibit cytokine secretion in the lipopolysaccharide (LPS)-stimulated macrophage cell line J774A.1. Results: Significant increases in the production of nitric oxide (NO) and tumor necrosis factor α(TNF-α) were found after the application of LPS for 24 h. Nifedipine, nicardipine and verapamil significantly inhibited LPS-induced NO secretion without causing changes in intracellular free calcium concentration. Diltiazem could not decrease the LPS-induced NO or TNF-α secretion levels. Only the dihydropyridine analogs, nifedipine and nicardipine, were able to reduce LPS-induced TNF-αsecretion. The inhibition of NO secretion could not be antagonized by the application of cAMP and cGMP analogs or serine/threonine protein kinase inhibitors. However, the inhibition of TNF-α secretion could be reduced by the application of the protein kinase inhibitors nifedipine and nicardipine. Thus, different intracellular pathways may be involved in the regulation of production and secretion of NO and TNF-αin endotoxin-activated macrophages. Conclusions: Because nifedipine and nicardipine can inhibit the induction of NO as well as TNF-α our results suggest that these are potential anti-inflammatory drugs. Thus, some calcium channel antagonists could be developed for use clinically as anti-inflammatory drugs.