Abstract: Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist–tricyclic antidepressant amitriptyline—significantly inhibits store-dependent Ca ²⁺ entry, induced by endoplasmic Ca ²⁺-ATPase inhibitors thapsigargin and cyclopiazonic acid, in rat peritoneal macrophages. The results suggest a possible involvement of sigma-1 receptors in the regulation of store-dependent Ca ²⁺ entry in macrophages.