The neurotoxic effects of kainic acid (KA) on developing neurons in the chick retina was investigated in an in vitro preparation. Eyecups from chick embroyos at 6 (E-6), 8, 10, 12, 14, 16, and 20 days of incubation and from chicks on day 1 posthatch (D-1) were exposed to different doses of KA for 30 min and then processed for light microscopy. Neurotoxic damage was evaluated by the presence of swollen cell bodies, containing pale cytoplasm and pyknotic nuclei. At E-8, amacrine cells first became sensitive to KA and displayed neurotoxic damage at a threshold concentration of 20 microM. Their sensitivity to KA increased over the following 4 days, so that by E-12 they attained a threshold sensitivity of 5.0 microM KA. At E-14, one third of the retinae showed amacrine cell damage at 0.5-2.0 microM KA, less than the threshold dose of 5.0 microM KA required at D-1. Bipolar cells first become sensitive to KA at E-12, at a threshold concentration of 5.0 microM. The threshold concentration decreased over the following 10 days: 2.0 microM at E-16, 1.0 microM at E-20, and 0.5 microM at D-1. At E-8 and E-10, horizontal cells were susceptible to a relatively high concentration of 80 microM KA. The sensitivity to KA is evident prior to the formation of photoreceptor input. These results indicate that amacrine and horizontal cells are susceptible to KA at an earlier age than bipolar cells. Both amacrine and bipolar cells exhibit an age-dependent relationship with the threshold concentration of KA required to cause neurotoxicity; in general, the older the embryo, the lower the dose of KA. However, the increased susceptibility of amacrine cells at E-14 suggests a transient hypersensitivity to KA during this period which may reflect an overproduction of the receptor-ionic channel complex necessary for KA to exert its effect.