Patches excised from fields CA1 and CA3 of the hippocampus were used to study AMPA receptor responses to repetitive application of brief pulses of agonist. AMPA receptors in field CA1 exhibited a larger degree of paired-pulse depression and a slower recovery rate from desensitization than those from CA3 patches. Responses became progressively smaller during a train of short pulses (4 at 100 Hz), an effect that was greater in CA1 than CA3 patches and that was blocked by a drug (cyclothiazide) that slows desensitization. Cyclothiazide also increased steady state currents during a long pulse of glutamate and had a lower EC50 for CA3 than CA1 AMPA receptors. These results suggest (i) that differences in the relative balance of flip vs. flop subunits affect the kinetic and pharmacological properties of AMPA receptors in vivo, and (ii) that the rate of recovery from desensitization may influence responses to the bursts of afferent activity commonly used to induce long-term potentiation.