The effect on systolic (SAP) and diastolic (DAP) arterial blood pressure of 5 mg mepindolol daily vs 12.5 mg hydrochlorothiazide daily vs 5 mg mepindolol plus 12.5 mg hydrochlorothiazide daily was evaluated in this multicenter study. After a 2-week washout period with placebo, 138 patients with mild to moderate essential hypertension (WHO Class I and II), homogeneous for age and blood pressure values, were randomly allocated to one of the three treatment groups. Arterial blood pressure and heart rate were obtained at the beginning and at the end of the washout placebo period, and after 2, 4, and 6 weeks of active treatment. At the beginning and at the end of the study, all patients underwent a thorough clinical and laboratory evaluation, including blood chemistry, electrocardiogram, and chest roentgenogram. A trend toward normalization of blood pressure was defined as a lowering of DAP to 90 mmHg or at least a 10-mmHg decrease from the control value. Statistical analysis was performed on all the data. After 6 weeks of treatment, SAP and DAP values were significantly reduced in 67% of the patients in all groups. In 71% of patients on mepindolol plus hydrochlorothiazide a particularly more marked decrease in DAP was observed. Mepindolol was well tolerated: side effects were generally mild and inconsequential. The results show that mepindolol, given as a single oral dose of 5 mg, is an effective agent in the treatment of mild to moderate essential hypertension. Because of its efficacy, the advantage of single daily administration, and lack of important side effects, it can increase compliance to therapy. Moreover the association of mepindolol plus hydrochlorothiazide appears to be safe and effective.