This self-matched control study aimed to compare the efficiency of two different regimens of active treatment: aspirin in low (100 mg daily) versus intermediate (500 mg daily) doses in abolishing angiotensin-converting enzyme inhibitor (ACEI)-induced cough. A dry bothersome cough is the most common adverse class effect of all angiotensin-converting enzyme inhibitors. Prostaglandins (PG) have been pinpointed as playing a leading role in the genesis of ACEI-associated cough. The role of different doses of the most commonly used PG inhibitor-aspirin-in ACEI cough modification was not yet elucidated. Of 350 consecutive ACEI-treated patients, we identified 34 (9.7%) nonsmoking ACEI-related coughers. Patients with lung disease, nonsteroidal anti-inflammatory drug (NSAID) treatment, and those who did not agree to participate in the study were excluded. In the remaining 14 ACEI coughers (eight men, six women; mean age, 63 +/- 11 years), the treatment was discontinued; the dry cough completely disappeared, but returned in all patients within 1 week after ACEI reintroduction. At the end of the rechallenge period, patients started a low dose of aspirin for 1 week, switching thereafter to the intermediate dose of aspirin for an additional week. On each visit the cough severity (CS, 0-4) and frequency (CF, 0-10) scores were registered. Low doses of aspirin were ineffective in suppressing ACEI-induced cough, whereas intermediate doses completely abolished cough in five patients and reduced coughing in all but one patient; CS and CF decreased, respectively, from 2.5 +/- 1.0 to 0.9 +/- 1.1, P < .002 and from 6.6 +/- 2.4 to 2.4 +/- 1.1, P < .0002. Overall, intermediate doses of aspirin beneficially modified cough scores in 13 (93%) patients, enabling nine (64%) to continue ACEI treatment. Aspirin did not influence blood pressure control either in hypertensives or in postinfarction patients. We conclude that intermediate but not low doses of aspirin probably can suppress ACEI-induced cough. These findings propose a new alternative therapeutic approach for patients with ACEI-related cough, especially those in whom ACEI treatment seems to be essential.