In addition to their effects on blood pressure, antihypertensive agents may produce additional effects on blood rheology and arterial compliance abnormalities which may play a role in target-organ damage. However, these effects may depend only on the specific pharmacological properties of certain antihypertensive agents, and may be partly unrelated to blood pressure lowering action. We compared the effects of nitrendipine 20 mg once daily to hydrochlorothiazide 25 mg once daily in 33 mildly to moderately hypertensive and otherwise healthy patients, in a double blind parallel group trial. Blood rheology (blood fibrinogen and protein concentrations, hematocrit, plasma viscosity and whole blood viscosity at shear rates 0.2 to 128 s-1, erythrocyte deformability and aggregation) and radial artery diameter and compliance (Nius I + Finapres) were measured at baseline and after 2 months of treatment. Both drugs produced similar blood pressure lowering. Blood viscosity increased for all shear rates in the hydrochlorothiazide group and decreased in the nitrendipine treated group. Erythrocyte deformability increased in the nitrendipine but not in the thiazide group. Radial artery diameter and compliance were not different between the two groups but there was a trend towards an increase in cross-sectional compliance in the hydrochlorothiazide group and towards a decrease in the nitrendipine group. Our data show that, in mildly hypertensive patients, blood pressure control by nitrendipine produced more favourable effects on relevant rheological variables than hydrochlorothiazide. Radial artery compliance changes tended to be altered also in opposite directions by the two agents. The significance and the clinical relevance of these effects may require further investigations.