A prospective, randomized, cross-over trial comparing the antihypertensive efficacy and biochemical changes during treatment with either hydrochlorothiazide (HTZ: 25 mg o.d.) or propranolol (PRO: 40 mg t.i.d.), included 55 mild to moderate hypertensives (diastolic blood pressures ranged from 90 to 110 mmHg), aged 25-65 years. Forty patients completed the study; during the first six months 20 of them (12 males and 8 females) were taking HTZ, and the remaining 20 (13 males and 7 females) PRO. After a one-week wash-out period, for the next six months the alternative drug was administered. Antihypertensive efficacy of both drugs was nearly equal: systolic and diastolic blood pressure significantly decreased already after the first month (approximately by 10%), and kept unchanged until the end of the study. The analyzed biochemical parameters, i.e. blood glucose, cholesterol, and triglycerides did not increase significantly, while serum potassium level remained almost unchanged during the trial. Furthermore, during PRO in group B, cholesterol significantly decreased (3rd month), as well as blood glucose during HTZ treatment (10th month). Only the uric acid level, although unsignificantly, increased in group A (from 326.2 to 365.3 +/- 125.2 on HTZ, and to 391.4 +/- 120.0 mumol/l on PRO). It is concluded that HTZ and PRO are comparably effective antihypertensives. During the long-term treatment in small doses these drugs do not induce significant biochemical disturbances.