To characterize the nature of kainate (KA) receptors distinct in the CA3 region of the hippocampus, properties of depolarizations induced by pulses of KA or AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) applied to dendrites of CA3 neurons with micropipettes were studied in thin transverse slices of the guinea pig hippocampus. KA induced depolarizations at negligible latencies only when administered to the most proximal dendritic areas. The depolarization was unaffected by tetrodotoxin or by a decrease in Ca2+ and an increase in Mg2+ concentrations. The declining slope of the KA-induced depolarization was significantly slower than that of the AMPA-induced depolarization. In comparison with the AMPA-induced depolarization, the KA-induced depolarization was much less susceptible to antagonists such as 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) and 1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI52466). 6, 7,8,9-Tetrahydro-5-nitro-1H-benz[g]indole-2,3-dione-3-oxime (NS-102) and (2S,4R)-4-methylglutamate (SYM 2081) were without effects. The threshold concentration of pressure-ejected KA to induce depolarizations was about 200 nM. Excitatory postsynaptic potentials elicited by mossy fiber stimulation were more potently suppressed by CNQX than by GYKI52466. These results indicate that receptors responsible for the slow KA depolarization in the CA3 region of the hippocampus are not AMPA receptors but KA receptors. They are localized in the most proximal part of the apical dendrite and distinct from those observed in primary cultures of hippocampal neurons.