One hundred and thirty five non-smoking hypertensive patients with ACE inhibitor cough confirmed by lisinopril rechallenge and placebo dechallenge were recruited into a double-blind random parallel-group comparison of losartan 50 mg, lisinopril 20 mg and hydrochlorothiazide 25 mg each given once daily for a maximum of 8 weeks. The aim of the study was to compare the incidence of cough with the angiotensin II antagonist losartan, the ACE inhibitor lisinopril and the hydrochlorothiazide in hypertensive patients with previous ACE inhibitor cough. Cough detected by self-administered questionnaire was the primary end-point, and cough frequency by visual analogue scale a secondary end-point. The incidence of cough with losartan (29%) was lower than that for lisinopril (72%, P < 0.01) and similar to that for hydrochlorothiazide (34%). Cough frequency by visual analogue scale was lower for losartan than lisinopril (P < 0.01) and similar to that for hydrochlorothiazide. The specific selective AT, angiotensin II receptor antagonist losartan is significantly less likely than lisinopril to cause cough in patients who previously have had ACE inhibitor cough. ACE inhibitor cough is likely to be related to non-specific kininase II inhibition.