Two first-line antihypertensive therapies for initiating treatment in hypertension were compared, the angiotensin-converting enzyme inhibitor (ACEI) zofenopril and the beta-blocker atenolol. The study was multi-centre and double-blind, and included 304 middle-aged to elderly patients with mild to moderate hypertension who were randomized to receive either zofenopril 30-60 mg once daily (od) or atenolol 50-100 mg od for 4 weeks with the possibility to an up-titration in non-responding patients. The higher dose level was then administered until 12 weeks after randomization. Blood pressures (BPs) were substantially reduced by either treatment, but after 4 weeks, the systolic and diastolic BP reductions were significantly greater (p < 0.05) with zofenopril (-15.6/-13.5 mmHg) compared with atenolol (-13.1/-11.8 mmHg). After 12 weeks and the possibility of dose up-titration, BP differences between treatments were no longer significant. However, control rates (sitting diastolic BP < 90 mmHg) for zofenopril remained significantly higher compared with atenolol. The number of subjects with adverse drug reactions possibly or probably related to the study medication was 14 (9.1%) in the zofenopril group and 30 (20.8%) in the atenolol group (p = 0.008). It is concluded that zofenopril as well as atenolol induces substantial reductions of diastolic BP in middle-aged to elderly patients with hypertension. However, the control rate when initiating antihypertensive therapy with zofenopril is higher than that for atenolol.