The beta-adrenoceptor blocking and diuretic properties of tienoxolol (150 mg and 300 mg) were investigated and compared to those of a placebo in a double-blind, cross-over trial in six healthy volunteers. Heart rate (HR), systolic and diastolic blood pressures, peak expiratory flow rate (PEFR) at rest and during vigorous exercise, plasma renin activity (PRA) and aldosterone levels at rest, and diuresis and urinary electrolyte excretion values were measured before and at intervals up to 24 h after oral administration of the drugs. In addition, the clearances of electrolytes, uric acid, and creatinine were calculated, as well as the fractional sodium excretion (Fe Na%) before and 4 h and 24 h after drug intake. Finally, tienoxolol plasma levels were measured. Tienoxolol significantly and dose-dependently reduced exercise-induced tachycardia. This effect started 1 h after drug administration, peaked between 4 h and 6 h (-12% and -17% from control values at 150 mg and 300 mg, respectively), and lasted at least 12 h. Resting HR was decreased at 300 mg (P less than 0.05), PRA was decreased at both doses (P less than 0.05), but PEFR was not drug-affected. 24-h cumulative sodium excretion was increased (+24% at 150 mg [NS], +38% at 300 mg [P less than 0.01]) as compared to placebo, and Fe Na% did not change, regardless of the dose administered. 24-h cumulative diuresis was moderately increased by tienoxolol (NS), whereas creatinine clearance rose after the 300-mg dose, suggesting that tienoxolol might increase glomerular filtration rate. Plasma aldosterone levels remained unchanged. Finally, the elimination half-life of tienoxolol was 7.5 h. Thus, in healthy volunteers, tienoxolol behaves as an early acting and relatively long-lasting selective beta 1-adrenoceptor blocking drug endowed with significant natriuretic properties.