OBJECTIVE To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. METHODS Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP > 95mmHg had the dosage, once daily, increased to 20mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in alpha-methyldopa (100 patients); beta-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). RESULTS At the end of the period without treatment, the blood pressure (BP), 165 +/- 16/105 +/- 7mmHg decreased significantly at 6th week to 144 +/- 15/91 +/- 9mmHg (p < 0.05 vs week 0) with further lowering to 139 +/- 13/86 +/- 7mmHg till the end of 12th week. BP response (DBP < or = 90mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were > or = 70% in patients with F compared to other drugs. CONCLUSIONS Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy.