These studies were undertaken to evaluate different manifestations of structural cardiovascular changes and the effects of antihypertensive therapy in essential hypertension. A meta-analysis of 109 studies that had examined the effect of different pharmacological blood pressure lowering regimens on left ventricular structure, examined by echocardiography, was undertaken to increase the statistical power, to resolve uncertainty and to improve the accuracy of estimation of the magnitude of effect. Strict preset criteria were applied. The effect of different drugs in monotherapy and in particular first line antihypertensive therapies were compared, using an analysis of covariance (ANCOVA). ACE-inhibitors, beta-blockers and calcium antagonists all reduced left ventricular mass (LVM) through a reduction in wall hypertrophy, the effect being most pronounced with ACE-inhibitors. Conversely, diuretics reduced LVM mainly through a reduction of left ventricular volume. Previously untreated males (n = 28, 86 kg, 46 years, 27 kg/m2) with non-malignant essential hypertension (supine diastolic blood pressure (DBP) > 95 mmHg 3-4 times (in triplicate) on placebo) were randomized to long-term double-blind treatment with enalapril (E) or hydrochlorothiazide (H). There were no significant differences between the groups at baseline. Vascular alterations in the retina (eyeground photo, refined grading), cardiac morphology (M-mode echocardiography, ASE), structural vascular changes of the hand (plethysmography, minimal resistance (Rmin)), total peripheral resistance ((TPR), calculated from dye-dilution) and blood pressure (intraarterial) were significantly interrelated at baseline except LVM and Rmin. After 6 months of therapy, E reduced the signs of vascular changes in the retina as well as Rmin in the hand circulation, while H did not change or increased these structural vascular changes. The blood pressure lowering effect of E (mainly through lowering of TPR) tended to be more pronounced, measured both intraarterially and indirectly, than that seen with H (mainly through lowering of cardiac output), however, there were no significant differences. LVM decreased progressively with E while the effect of H was non-significant. E reduced wall thickness but not left ventricular diameter and also improved left ventricular distensibility significantly. The effect on cardiac morphology was significantly different between therapies when taking change in blood pressure into account. After the longest follow-up on monotherapy (18 months) E had reduced LVM by 2.7 g/mmHg and H (14 months) by 1.3 g/mmHg (significant for E only). In univariate analysis the changes in cardiovascular structure were significantly related to the changes in the Renin-Angiotensin-Aldosterone System (RAAS).(ABSTRACT TRUNCATED AT 400 WORDS)