1 The effect of tetraphenylboron (TPB) were studied on the frog sciatic nerve-sartorius muscle preparation. 2 TPB (0.01-1 mM) blocked indirectly elicited twitches of the preparation. 3 TPB (0.01-0.1 mM) produced no depolarization but lowered membrane resistance. TPB increased miniature endplate potential (m.e.p.p.) frequency, the rate of rise of the endplate potential (e.p.p.), and slowed the rate of rise and rate of fall of the muscle action potential. 4 In Mg2+ solutions the quantal content of e.p.ps was initially increased by TPB (0.01 mM). This was followed by a decrease of e.p.p. and m.e.p.p. amplitudes, accompanied by a lack of e.p.p. failures. 5 Larger concentrations of TPB (0.1 mM) produced an increase in e.p.p. amplitude followed by the sudden abolition of e.p.ps. This effect was associated with abolition of the nerve terminal spike. 6 TPB (0.1 mM) exhibited no postjunctional blocking action. 7 The results indicate that TPB acts prejunctionally, initially causing an increased release of acetylcholine. Subsequently, transmitter output is reduced by a reduction of quantal size.