The aortic nerve was used to study the blocking action of procaine and bupivacaine on natural spike activity. In anesthetized cats, a segment of the aortic nerve was placed in a perfusion chamber and exposed to increasing drug concentrations, varying pH, while temperature remained constant. Total nerve activity was recorded continuously, and its change was related to drug concentration. The half-time of recovery following drug wash-out was also determined. At pH 7.4, the minimal blocking concentration was 0.5 X 10(-3) mol/l for procaine and 0.05 X 10(-3) mol/l for bupivacaine, the half-times of recovery 1.4 and 3.0 min, respectively. Procaine and bupivacaine reversibly blocked natural spike activity at the same concentrations as they blocked electrically evoked activity. The aortic nerve, whose physiologic spike traffic can be followed continuously for hours, may be used to advantage for studying the long-term effects of local anesthetics in vivo.