1. The effects of sodium salicylate on the frequency of miniature endplate potentials (m.e.p.ps) and on the quantal content of endplate potentials (e.p.ps) in mouse diaphragm muscles at 36 degrees C and 24 degrees C were studied by conventional microelectrode techniques. 2. At 36 degrees C, salicylate (10 mM) elevated the frequency of m.e.p.ps in a manner which was insensitive to [Mg2+]0 and independent of the presence of [Ca2+]0. Lowering the temperature to 24 degrees C abolished the stimulating effect. 2,4-Dinitrophenol (10 microM) had similar effects at 36 degrees C and these disappeared at 24 degrees C. All subsequent experiments were performed at 24 degrees C. 3. Salicylate (10 mM) further increased the frequency (F) of m.e.p.ps stimulated by [Ca2+]0 in a depolarizing solution. When [Ca2+]0 was varied in the absence of salicylate, a linear relationship between ln(F) and ln([ CA2+]0) was obtained. Salicylate shifted this relationship to the left, with respect to the control, without altering the slope. 4. Salicylate (5 mM) also increased the quantal content (m) of e.p.ps in a solution that contained 5 mM Mg2+, in a concentration-dependent fashion. As [Ca2+]0 was varied in the absence of salicylate, a linear relationship between ln(m) and ln[(Ca2+]0) was observed. Salicylate shifted this linear relationship to the left, with respect to the control, without altering the slope. Doubling the concentration of [Mg2+]0 antagonized this effect of salicylate on the quantal content of e.p.ps. 5. These results indicate that salicylate enhances the effect of changing [Ca2+]0. Salicylate probably facilitates the entry of Ca2+ into the nerve terminal or sensitizes the process that is regulated by Ca2 , thereby stimulating the release of transmitter. Surface negative charges may have an important role in the effect of [Ca22]0.