Application of L-glutamate (L-glu) to particular neurons (G-H cells) in the esophageal ganglia of Onchidium produced hyperpolarization associated with an increase in K+ permeability. The reversal potential (Erev) for this response, was -60 mV. The ED50, an indicator of affinity between L-glu and its receptive site, was 5.3 mM, and the Hill coefficient n, an indicator of cooperativity, was 2. Other chemicals, structurally analogous to L-glu, were also examined on G-H cells. The responses of L-aspartate were similar to those of L-glu with respect to Erev, ED50, and n. However, the G-H cells responded differently to D-glutamate (D-glu) and kainic acid. The D-glu response had an Erev = -37.5 mV, ED50 = 29.4 mM, and n = 1; that of kainic acid had an Erev = 0 mV, ED50 = 1.5 mM, and n = 1. L-glutamine and GABA elicited very small responses, amplitudes of which were less than 10% of the L-glu response. The structure-activity relationship between L-glu and its analogues, estimated from Erev, ED50, and Hill coefficient during each drug application, indicates that the presence of alpha-NH2, alpha-COOH, and gamma-COOH groups is essential for the L-glu response and that the response characteristics may be closely related to the relative positions of these groups.