Antihypertensive therapy has been thought to be a life-long treatment. Nevertheless, antihypertensive medication may be discontinued in a substantial proportion of hypertensive patients at least for some time. The current study focused on predictors for the development of elevated blood pressure levels after discontinuation of antihypertensive drug therapy. In an open, prospective study, 88 white male patients with newly discovered essential hypertension (age 42 ± 7 years) were tested at baseline. Blood pressure was measured in various situations (at work, at rest, before and during treatment, and at follow-up), and the hemodynamic profile at rest and cardiovascular response patterns during stress tests were evaluated. Left ventricular mass and other cardiovascular risk factors were also carefully determined. After 6 months of strict blood pressure control ( < 140/90 mm Hg), they were treated by their primary care physician (mean duration of antihypertensive therapy 1.3 ± 1.7 years). After 6 years, 37 patients were still on antihypertensive therapy, but 19 of the 37 had blood pressure values ≧ 160/95 mm Hg. In 51 patients, therapy was discontinued: 29 were hypertensive, 15 were borderline hypertensive and 7 were normotensive. Relapse of hypertensive blood pressure in these 51 patients off therapy was predicted by resting blood pressure values before therapy (138 ± 11/91 ± 5 vs. 131 ± 11/85 ± 7 mm Hg, p < 0.05/0.01), cardiac output at rest (7.5 ± 1.9 vs. 6.2 ± 2.1 1/min, p < 0.05), total peripheral resistance (20 ± 9 vs. 14 ± 4 U, p < 0.05), increased heart rate during ergometry (50 ± 8 vs. 44 ± 6 b.p.m., p < 0.05) and left ventricular mass determined by echocardiography(212 ± 60 vs. 189 ± 44g, p < 0.01). There was no difference in age, blood pressure levels before and during treatment, the number of consultations with the primary care physician or cardiovascular risk factor profiles. In conclusion, intermittent rather than life-long antihypertensive treatment may be possible in hypertensive patients with low resting blood pressure, high cardiac output, low total peripheral resistance and low left ventricular mass.