After a single-blind, 4-week placebo run-in period. 161 patients were randomized to trandolapril 2 mg once daily (n = 54). nifedipine slow-release (SR) 20 mg twice daily (n = 55), or a combination of both drugs (n = 52) for 16 weeks. Morning predosing supine diastolic blood pressure (DBP) was the primary efficacy measurement. After 16 weeks the intention-to-treat analysis showed no significant difference in supine DBP (mean ± SEM) between trandolapril (-12.4 ± 1.5 mm Hg) and nifedipine SR (-15.3 ± 1.4 mm Hg: p = 0.1). However, the combination therapy was more effective (-18.9 ± 1.3 mm Hg). Normalized blood pressure at 16 weeks was seen with 54% on trandolapril, 63% on nifedipine SR, and 77% on the combination. Adverse events, possibly related to drug, were more common with nifedipine SR (34%) than with trandolapril (17%: p < 0.05), and in comparison with the combination (21%). Drug-related treatment emergent events. reported by more than 3% of patients (fatigue, palpitations, edema, migraine), were seen only in the nifedipine SR and combination groups. Trandolapril 2 mg proved a well-tolerated and effective antihypertensive agent, comparable to nifedipine SR 40 mg. Furthermore, the combination of the two drugs was shown to enhance the antihypertensive effect of the two compounds alone. Adverse events were less common with trandolapril and the combination than with nifedipine SR alone.