Short-term (15 minutes) in vitro exposure to kainic acid (KA), a rigid structural analog of L-glutamic acid (Glu), caused two morphologically distinct neuronal lesions in retinas of several species. In rabbit retina, one type of lesion was characterized by rapid swelling after exposure to low concentrations of KA (10(-4)M). This lesion was observed in elements of both plexiform layers and, more specifically, in cell bodies and neurites of horizontal cells that contact cones. A few cell bodies from the amacrine cell layer showed some limited swelling. The swelling was completely blocked when sodium was removed from the incubation medium. The second type of lesion was generally seen after longer exposures of after exposure to higher concentrations of KA and was evidenced by degeneration of neurons in the amacrine and ganglion cell layers. One exception was noted in that a few cells from the ganglion cell layer degenerated even under low exposure conditions. The second type of lesion was not blocked by removal of sodium ions. Photoreceptor cells appeared resistant to all effects of KA. The results suggest that a correlation may exist between certain KA-induced lesions of the retina and putative glutamoreceptive neurons. At the same time, the two types of retinal lesions produced by KA are morphologically and chemically differentiable and may be useful in elucidating the differences between specific, Glu-related toxicity and nonspecific toxicity of KA.