OBJECTIVE A high prevalence of associated metabolic cardiovascular risk factors is often observed among hypertensive subjects. The aim of the present study was to assess the effects of 1-2 mg/day of rilmenidine, a centrally acting antihypertensive agent with selectivity for I(1) imidazoline receptors, vs. 2.5-5 mg/twice daily of isradipine, a dihydropyridine calcium channel blocker, in hypertensive patients with features of the metabolic syndrome. METHODS In this 6-month multicentre, comparative, double-blind, parallel group study, the primary objective was to assess the effects of the treatments on blood pressure (BP); the secondary endpoints were to assess glucose and lipid metabolism, in addition to clinical and biological tolerability. In non-responder patients, dose adjustment was possible from the first month and adding a diuretic from the third month. RESULTS Of an intention-to-treat population of 93 patients, 84 per protocol patients completed the study: 42 in the rilmenidine group and 42 in the isradipine group. BP decreased significantly (p < 0.001) and similarly in both groups (systolic blood pressure, SBP: -16.0 +/- 17.2 mmHg and -15.0 +/- 13.0 mmHg, and diastolic blood pressure, DBP: -9.0 +/- 9.4 mmHg and -9.0 +/- 8.7 mmHg with rilmenidine and isradipine, respectively). Normalisation (DBP < 90 mmHg and SBP < 140 mmHg) and response (normalisation or decrease in SBP >or= 20 mmHg or decrease in DBP >or= 10 mmHg) rates were respectively 57% and 72% with rilmenidine and 64% and 79% with isradipine (NS between groups). The effects of the treatments on both glucose and lipid metabolism were comparable: no significant difference from baseline was observed on the main parameters including insulin sensitivity indexes. The two treatments appeared to be well tolerated throughout the study, with no serious adverse reaction reported in the rilmenidine group and one serious adverse event in the isradipine group (a perimalleolar oedema), leading to withdrawal from the study for the affected patient. CONCLUSIONS This study suggests that in hypertensive patients with metabolic disorders, rilmenidine is an effective antihypertensive treatment, comparable to isradipine, with metabolic neutrality and a good tolerance profile.