1. The action of gamma-aminobutyric acid (GABA) on the hippocampal pyramidal cells was studied by intracellular recordings using an in vitro slice preparation. 2. Orthodromic tetanic stimulation induced dramatic modifications of the GABA response. Initial hyperpolarizing GABA responses were observed to invert to depolarizations following the tetanic shock. 3. The hyperpolarizing and depolarizing GABA responses exhibited differential sensitivity to GABA and bicuculline. Application of low concentrations of GABA predominantly activated the hyperpolarizing response. Activation of depolarizing response in both the dendrites and somata required a larger quantity of GABA. Bicuculline antagonized both the hyperpolarizing and depolarizing responses; however, the agent appeared to exert a stronger influence on the depolarizing response. At the concentration of 10(-5) M, bicuculline completely blocked the depolarizing response while the hyperpolarizing response was only suppressed by 50%. 4. During prolonged periods of GABA application (10 s or more), the GABA-induced conductance increase was not maintained, suggesting that the GABA response underwent desensitization. The results also suggest that the desensitization process affected both the hyperpolarizing and depolarizing responses. 5. The depolarizing response elicited by GABA was facilitated by increasing the extracellular potassium concentration. 6. It is possible that the modification of the GABA response following tetanic stimulation is in part caused by the desensitization of the GABA response and an accumulation of extracellular K+ and GABA.