A grease-gap method for studying the pharmacology of CA1 hippocampal pyramidal cells was developed with use of rat hippocampal slices that included only area CA1 and the retrohippocampal area. These slices were transferred to a two-compartment superfusion chamber and the pyramidal cell bodies in area CA1 were separated from their axons in the subiculum with a grease barrier. The CA1 pyramidal cells were depolarized relative to their axons by superfusion with N-methyl-D-aspartate (NMDA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and L-glutamate. NMDA was unusually potent in the CA1-subiculum slice compared to other preparations. The NMDA receptor antagonists D(-)-2-amino-5-phosphonovalerate (D-AP5), phencyclidine and Mg2+ shifted the NMDA dose-response curve to the right in a parallel manner. Similarly, the quisqualate receptor antagonist pentobarbitone shifted the AMPA dose-response curve to the right. Schild plots for these antagonists had slopes insignificantly different from 1. These results are consistent with the presence of a substantial NMDA receptor reserve on CA1 pyramidal cells. They are also in line with the high density of excitatory amino acid receptors on CA1 hippocampal pyramidal cells and with the known pharmacological properties of these receptors. Grease-gap studies on the CA1-subiculum slice fill the need for a means of obtaining quantitative pharmacological data on CA1 pyramidal cells.