Background: Endothelin (ET) -1 was found to participate in the pathogenesis of bronchial asthma. At present, there is no information regarding the role of ET-1 in the pathophysiology of atopic dermatitis (AD). Objective: We assessed blood ET-1 levels during the exacerbation of AD and during the 4 months postexacerbation period, to assess the relationships between blood ET-1 levels and clinical severity of AD and pruritus. Methods: Patients with AD and during exacerbation were recruited from the dermatology department at the Chita Medical Academy (Chita, Russia). Objective Severity Scoring of Atopic Dermatitis index, itch intensity, plasma concentrations of ET-1, and serum total immunoglobulin E levels were measured at study entry and after 4 months. Results: Eighty-two patients with AD, 35 women (45.1%) and 47 men (54.9%), mean (SD) age of 42.2 ± 11.5 years were included. Thirty healthy volunteers served as controls. The mean (SD) objective Severity Scoring of Atopic Dermatitis index score during AD exacerbation was 48.8 ± 19.4 and at the 4 months postexacerbation period was 16.1 ± 8.3 (p < 0.01). Mean (SD) itch score during AD exacerbation was 6.9 ± 1.9 and, at 4 months postexacerbation was 2.6 ± 0.7 (p < 0.01). Mean (SD) plasma levels of ET-1 in patients with AD (0.74 ± 0.45 fmol/mL) were significantly higher than in healthy subjects (0.43 ± 0.24 fmol/mL) (p < 0.001). Significant correlations were found between plasma ET-1 levels with the objective Severity Scoring of Atopic Dermatitis index (r = 0.51; p < 0.001), Itch severity (r = 0.62; p < 0.001), and with serum immunoglobulin E levels (r = 0.63; p < 0.001) at the exacerbation time point in patients with AD. Conclusion: During AD exacerbation, plasma ET-1 levels were elevated and were positively correlated with AD clinical severity, itch intensity, and serum IgE levels.