The isometric tension developed in response to diffuse application of acetylcholine was recorded in intact soleus muscles of the rat. Purified bacterial phospholipases of the C type, which hydrolyse either phosphatidylinositol or phosphatidylcholine, increased the acetylcholine contracture responses of the muscles. Sciatic nerve cytosol which had been purified over 8-fold with respect to phosphatidylinositol phospholipase C activity also increased these responses. The effect of phospholipase C on the miniature endplate potentials and neurally evoked endplate potentials was investigated in mouse diaphragm in vitro. The amplitude of both the miniature endplate potentials and the evoked endplate potentials was increased by the enzyme. The resting membrane potential, the effective input resistance and the frequency of miniature endplate potentials were not significantly altered by concentrations of the enzyme which increased the endplate responses. It is suggested that phospholipase C could have a trophic role at the neuromuscular junction.