1. In a placebo-controlled double-blind cross-over study lasting 6 weeks, twenty patients with essential hypertension were treated with placebo for 2 weeks followed by oral cilazapril 2.5 mg once a day or oral indomethacin 50 mg twice daily for 2 weeks. Afterwards they received the combination of both drugs for a further 2 weeks. 2. Cilazapril significantly lowered systolic and diastolic blood pressure for a period of 24 h post administration. 3. Indomethacin significantly attenuated the antihypertensive activity of cilazapril. This was more pronounced in those patients who were treated for the initial 2 weeks with indomethacin plus placebo (and subsequently with cilazapril in addition) than in the subjects who first received cilazapril plus placebo and then the combination. 4. Correspondingly the decrease of plasma renin activity (PRA) and urinary prostaglandin excretion (PGE2) was more pronounced in those patients treated initially with indomethacin. 5. The effect of indomethacin on the antihypertensive effect of cilazapril appears to depend upon the sequence of drug administration.