To find out what type of therapy was better for restoration of 24 hour blood pressure (BP) rhythm and impaired function of vascular endothelium, and to determine preferential therapy for patients with severe endothelial dysfunction.We performed ambulatory blood pressure monitoring and assessments of endothelial dependent (flow mediated-FM) and endothelial independent (nitroglycerine) dilatation of forearm artery (DFA) in patients with stage I-III essential hypertension. In a randomized comparative cross-over study 76 patients (mean age 49.2 +/- 6.2 years) received indapamide retard 1.5 mg and enalapril 20 mg for 24 weeks.Hypotensive effect of both drugs was identical (indapamide lowered systolic/diastolic BP by 13.6/12.0% and 12.9/9.9%, enalapril lowered BP by 14/14.6% and 13.2/12.9%). BP rhythm was better transformed by treatment with indapamide: nocturnal fall of mean BP increased on indapamide from 8.1 +/- 6.9% at baseline to 12.8 +/- 5.0% after treatment, p=0.007, and on enalapril from 11.8 +/- 7.9% at baseline to 10.4 +/- 6.2% after treatment, p=0.2. Indapamide and enalapril significantly augmented FM DFA (from 4.7 +/- 2.8% to 9.03 +/- 3.47%, p < 0.001, and from 4.6 +/- 2.2% to 10.9 +/- 3.5%, p < 0.001, respectively). All patients were divided into 2 groups: with baseline FM DFA - 2.5% (group I, n=59) and < 2.5% (group II, n=16). In group II indapamide lowered BP more effectively than enalapril ( - 10.2/ - 9.1% and - 5.5/ - 5.2%, p < 0,01/0.01, respectively).Both indapamide retard 1.5 mg and enalapril 20 mg exerted normalizing action on endothelium dependent DFA. However indapamide transformed 24 hour BP profile better than enalapril. Hypotensive therapy with indapamide was more effective than therapy with enalapril in patients with more pronouncedly disturbed FM arterial vasodilatation. This can be used in selection of a preparation in patients with impaired FM vasodilatation.