These experiments examined the relationship between behavioral and electrophysiologic signs of neuromuscular dysfunction in rats with zinc pyridinethione (ZPT)-induced neurotoxicity. ZPT added to the diet of adult rats at 50 ppm produced a moderate (approximately 200 g) reduction in forelimb and hindlimb grip strength which occurred during the second week of dosing. Other behavioral tests of peripheral nervous system toxicity were affected inconsistently. Electrophysiologic changes included a marked (maximum 95%) reduction of indirect muscle-evoked potential (M-wave) and a decrement (maximum 30%) during repetitive M-wave elicitation. Electrophysiologic changes were greater in hindlimb than in forelimb. Needle electromyography revealed denervation potentials in ZPT-treated rats which appeared after M-wave changes and recovered faster than did M-wave amplitude. Caudal nerve conduction velocity was unaffected, indicating that peripheral neurotoxic effects were confined to the neuromuscular junction. When ZPT exposure was discontinued, grip strength recovered in about 1 week. In contrast, electrophysiologic measures required 42 days to recover completely. These results indicate that deficits in neuromuscular junction physiology are a sensitive index of ZPT-related distal axonopathy.