A, Roppolo JR, de Groat WC, Tai C. Conduction block of mammalian myelinated nerve by local cooling to 15-30°C after a brief heating. J Neurophysiol 115: 1436 -1445, 2016. First published January 6, 2016 doi:10.1152/jn.00954.2015This study aimed at understanding thermal effects on nerve conduction and developing new methods to produce a reversible thermal block of axonal conduction in mammalian myelinated nerves. In 13 cats under ␣-chloralose anesthesia, conduction block of pudendal nerves (n ϭ 20) by cooling (5-30°C) or heating (42-54°C) a small segment (9 mm) of the nerve was monitored by the urethral striated muscle contractions and increases in intraurethral pressure induced by intermittent (5 s on and 20 s off) electrical stimulation (50 Hz, 0.2 ms) of the nerve. Cold block was observed at 5-15°C while heat block occurred at 50 -54°C. A complete cold block up to 10 min was fully reversible, but a complete heat block was only reversible when the heating duration was less than 1.3 Ϯ 0.1 min. A brief (Ͻ1 min) reversible complete heat block at 50 -54°C or 15 min of nonblock mild heating at 46 -48°C significantly increased the cold block temperature to 15-30°C. The effect of heating on cold block fully reversed within ϳ40 min. This study discovered a novel method to block mammalian myelinated nerves at 15-30°C, providing the possibility to develop an implantable device to block axonal conduction and treat many chronic disorders. The effect of heating on cold block is of considerable interest because it raises many basic scientific questions that may help reveal the mechanisms underlying cold or heat block of axonal conduction.