Objective: The present study investigated the presence of ET‐1 in gingival crevicular fluid (GCF) from patients with periodontitis, and the expression of endothelins (ETs) and their receptors mRNA in cultured cells from human periodontal tissues.Background: ET was originally discovered as a potent vasoconstrictive peptide from endothelial cells. It has been reported that ETs are produced by various cells besides endothelial cells. ETs are related to inflammatory and sclerotic lesions, such as arteriolosclerosis and hepatic cirrhosis. Therefore, ETs may be involved in periodontal disease. However, the roles of ETs in development and progression of periodontal disease are not clear.Methods: ET‐1 released from the cultured cells was measured by enzyme‐linked immunosorbent assay. mRNA expressions for ETs and their receptors were examined by reverse transcription‐polymerase chain reaction and Northern blotting analysis.Results: ET‐1 levels in GCF from patients with periodontitis were higher than those from healthy subjects. Human gingival keratinocytes (HGK) expressed mRNA for ETs and their receptors, ET‐Ar and ET‐Br. ET‐1 mRNA expression and ET‐1 peptide production from HGK were enhanced by interleukin‐1β and tumor necrosis factor‐α.Conclusions: These results suggest that ET‐1 plays a significant role in periodontal disease.