Adenosine is a potent modulator of transmitter release at a variety of synapses. The adenosine A1 receptor is assumed to reside in presynaptic terminals and to function as a negative autoreceptor. How adenosine reduces transmitter release is uncertain; it may reduce the calcium influx during nerve terminal depolarization by either activating K+ currents or inhibiting Ca2+ currents, although other mechanisms have been proposed. We have directly measured intracellular Ca2+ concentrations of giant pre-synaptic terminals in the chick ciliary ganglion. We report here that adenosine inhibited the nerve-evoked Ca2+ influx in the terminal by activating A1 receptors. Reduced Ca2+ influx was due largely to inhibition of omega-conotoxin GVIA-sensitive Ca2+ channels in the presynaptic terminal.