To determine the beta-adrenoceptor subtype controlling renin release from the kidneys, several beta-adrenoceptor subtype selective agonists and antagonists were administered to 15 healthy volunteers. While isoprenaline infusion (1, 2 and 4 micrograms/min for 5 min each) markedly increased plasma renin activity (PRA), the beta 2-selective agonist fenoterol failed to change PRA. The isoprenaline induced rise in PRA could be completely prevented by the beta 1-selective antagonists metoprolol (10 mg i.v. 45 min prior to isoprenaline infusion) and betaxolol (5 mg i.v. 45 min prior to infusion) indicating that renin release is mediated by beta 1-adrenoceptors. Binding studies with the highly specific beta-adrenoceptor radioligand (+/-)-125iodocyanopindolol demonstrated that membranes from human kidney cortical slices contain predominantly, if not exclusively, beta 1-adrenoceptors. These in vivo and in vitro results support the view that the beta-adrenoceptor mediating renin release from the human kidney is of the beta 1-subtype.