2,4-Dichlorophenoxyacetic acid (2,4-D), a common herbicide, was administered to rats (100 mg/kg, i.p.) during 24 days to determine whether or not it is toxic to regenerating peripheral nerve and reinnervating muscle. The peroneal nerve was crushed 1 cm proximal to the extensor digitorum longus muscle and recordings made in vivo after 1 to 24 days. Functional reinnervation was observed by day 10 and recovery was similar in rats receiving 2,4-D or vehicle. Distal motor latencies and muscle action potentials returned toward normal during the 24 days in a similar manner in 2,4-D and controls. Isometric twitch tensions per muscle weight on indirect stimulation returned to intact values by 17 days, but in the 2,4-D animals they became larger (P less than 0.01) than controls by day 24. The twitch:tetanus ratios were increased at day 10 and returned toward normal values in the controls but remained increased (P less than 0.01) in the 2,4-D animals at 24 days. Similar results were obtained on direct muscle stimulation. The data suggest that 2,4-D is not toxic to nerve during regeneration or muscle reinnervation in the rat, but that it does affect both twitch and tetanus tensions suggesting proliferation as well as disruption of myofibrils.