The acute renal effects of xamoterol, a partial beta 1-agonist, were studied in 12 patients with congestive heart failure (NYHA II-III) in stable condition on diuretic therapy for at least 6 weeks. Each patient was given a single intravenous infusion of xamoterol (0.2 mg/kg) or placebo in random order 2 weeks apart. Using constant infusion and lithium clearance techniques, clearance and excretion measurements were made in the supine position at 30- to 60-min intervals before, during, and up to 6 hours after infusion. Blood pressure, heart rate, renal plasma flow, glomerular filtration rate, and urinary flow rate remained unchanged, but xamoterol lowered sodium excretion by 30% (p < 0.05). The decrease started 120 minutes after infusion. Proximal reabsorption of sodium increased after xamoterol infusion, whereas plasma values of aldosterone and angiotensin II were unaffected. It is concluded that the acute renal effects of xamoterol imply an impaired sodium excretion determined by the tubular actions of the drug. The present results suggest that xamoterol may aggravate one of the important abnormalities intrinsic to the pathology of congestive heart failure. These findings are in contrast to the beneficial effects of xamoterol demonstrated in many clinical trials where xamoterol was given orally for a longer period.