The effect of lignocaine (0.01-100 micrograms.ml-1) on amplitude of indirectly and directly-elicited twitch contractions and on contractures produced by acetylcholine (ACh) (0.1-10 mM) and tetraethylammonium (TEA) (1.2-12 mM) was studied in isolated biventer cervicis skeletal muscle of the chick. Lignocaine (0.01-0.9 microgram.ml-1) increased the amplitude of the indirectly-elicited twitch contractions. At high concentrations (10-100 micrograms.ml-1), lignocaine decreased or blocked the twitch tension and produced a contracture in the chick skeletal muscle. Lignocaine also reduced or blocked the directly-elicited twitch contractions in a dose-dependent manner. Lignocaine (10 micrograms.ml-1) reduced the ACh-induced contracture whereas it increased that produced by TEA. Physostigmine (2 micrograms.ml-1) increased the stimulating effect of lignocaine, at low concentrations. However, repeated exposures to lignocaine followed by physostigmine resulted in both increase and decrease in the indirectly-elicited twitch contractions. It was concluded that lignocaine had a dual action at the neuromuscular junction. In low concentrations, lignocaine increases the twitch tension, possibly by an anticholinesterase action, and in high concentrations it reduces or blocks the twitch tension, produces a contracture in the muscle, and reduces the ACh-induced contractures, whereas it increases the TEA-induced responses. Some of these effects of lignocaine may be interpreted in terms of effects on excitation-contraction coupling in muscle.