"Successive action potentials in a pre-synaptic axon terminal often evoke responses of increasing amplitude in the post-synaptic cell. This phenomenon, called facilitation, is of interest to physiologists for several reasons. [...] Facilitation at the squid giant synapse has been noted by other workers but has not been extensively quantified [....] In the present experiments, solutions of low calcium concentrations were used to reduce transmitter release to subthreshold levels and to enhance the detection of facilitation. I have shown that the magnitude, time course of decay and summation of facilitation are similar in squid and other animals. This result lends generality to findings in the squid concerning the mechanism of facilitation discussed in this and the following chapter. [...] Various hypotheses for the mechanism of facilitation involve changes in major factors governing transmitter release such as pre-synaptic depolarization and the availability of calcium ions. [...] In order to test these hypotheses, it is necessary to directly measure and modify these parameters in the pre-synaptic terminal. I chose the squid giant synapse to study facilitation because its extremely large size enables one, by placing microelectrodes directly in the pre-synaptic terminal, to measure and manipulate some of the above variables (Takeuchi and Takeuchi, 1962; Miledi, 1973; Llinas and Nicholson, 1975). This preparation was used to test the residual-calcium hypothesis by altering extracellular calcium concentration and temperature, and to test the membrane-potential hypotheses by recording and manipulating presynaptic membrane potentials"--Leaves 1-3