Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor antagonist neuroleptic chlorpromazine significantly inhibits glutoxim- and molixan-induced Ca²⁺ responses and Ca²⁺ responses induced by endoplasmic reticulum Са²⁺-ATPase inhibitors thapsigargin and cyclopiazonic acid in rat peritoneal macrophages. The results suggest the involvement of sigma-1 receptors in the signaling cascade induced by glutoxim or molixan and leading to intracellular Ca²⁺ concentration increase and in the regulation of store-dependent Ca²⁺ entry in macrophages.