Intrinsic heart rate was measured in 19 dogs in 76 experiments after autonomic blockade, using various forms of anesthesia. Measurements were made in conscious dogs (n = 16) and in dogs in neuroleptanesthesia (n = 54) or under pentobarbital sodium (n = 6). Temperature, arterial pH, and blood gases were kept within narrow limits. Adrenergic blockade was achieved by phenoxybenzamine (2 mg X kg-1) and propranolol (2 mg X kg-1, followed by 2 mg X kg-1 X h-1). The parasympathetic system was blocked either by atropine (0.5 mg X kg-1, followed by 0.5 mg X kg-1 X h-1) and hexamethonium (20 mg X kg-1, followed by 10 mg X kg-1 X h-1) or by atropine and bilateral cervical vagotomy. Administration of hexamethonium or vagotomy was needed to block the vagal cardioacceleration unmasked by the administration of muscarinic blocking agents in conscious dogs and in dogs in neuroleptanesthesia. The mean denervated heart rate was 142.8 beats/min. This value is higher than that reported for surgically denervated hearts, the difference very likely reflecting the activity of the intact parasympathetic intrinsic cardiac innervation in surgical preparations. The estimated intraindividual and interindividual SD were 9.7 and 19.4 beats/min, respectively. The highly significant interindividual variation (P less than 0.01) contradicts the concept of an intrinsic heart rate as a practically constant species-dependent quantity.