1. The action of adenosine on neuromuscular transmission has been studied on the rat phrenic nerve-diaphragm preparation.2. Adenosine (0.025-10 mM) reversibly reduced the quantum content of end-plate potentials and the frequency of miniature end-plate potentials to about half the control values in preparations in which transmission was blocked with high Mg(2+) and/or low Ca(2+) concentrations. Where transmission was blocked with tubocurarine, the amplitude of end-plate potentials was reduced to about half the control values by adenosine.3. In solutions with very low Ca(2+) concentrations (no added Ca(2+) and 1 mM-EGTA) adenosine had a smaller effect on the frequency of miniature end-plate potentials.4. The effect of adenosine (0.025 and 0.05 mM) was abolished by theophylline (1.8 mM).5. The results are discussed in relation to the increase in cyclic AMP in brain slices caused by adenosine and the abolition of this effect by theophylline (Sattin & Rall, 1970).