1. Heterosynaptic facilitation was defined as an increase of amplitude of a test excitatory post-synaptic potential (EPSP) after the activation of a pathway (heterosynaptic pathway) different from that which produced the test EPSP. This phenomenon has been studied in Aplysia central nervous system under conditions which excluded the participation of post-tetanic potentiation.2. A unitary test was produced in the left and right giant cells, by indirect stimulation of an interneurone located in the peri-oesophageal ring.3. During heterosynaptic stimulation, orthodromic and antidromic activation of the test interneurone was prevented by (1) isolating the synaptic afferent region of the test interneurone from the tested synapse on the right giant cell by a sucrose block applied on the left pleurovisceral connective, and (2) using physiological stimulation of a piece of skin as a heterosynaptic stimulus. Under these conditions which prevented any firing in the test interneurone, heterosynaptic facilitation is observed as a 200% increase of amplitude of the test EPSP in the right cell which lasted more than 15 min. When instead of the physiological stimulus a supramaximal electrical stimulation of the nerves afferent to the abdominal ganglion was used, the increase of amplitude of the test EPSP could reach as much as 500% of its original amplitude. The effectiveness of such heterosynaptic stimulus was smaller when it was applied in the absence of a block of the left pleuro-visceral connective.4. It was possible to produce heterosynaptic facilitation when the preparation was cooled to 7-9 degrees C or if Li(+) replaced Na(+) in the medium. Both of these changes suppressed post-tetanic potentiation.5. It was concluded that heterosynaptic facilitation is a phenomenon different from post-tetanic potentiation. Heterosynaptic facilitation is similar to heterosynaptic inhibition seen in other cells in the same preparation, except for the polarity of action. Both phenomena seem to result from comparable mechanisms, probably acting on the quantity of transmitter released.