Surface and depth electroencephalograms (EEGs) were studied after intravenous injections of kainic acid (KA). High frequency oscillations and spikes appeared in the hippocampus at a dose (1 mg per kilogram) that did not affect other structures. Higher doses (greater than or equal to 4 mg per kilogram) led to electrical seizures in limbic structures, similar to those in temporal lobe epilepsy. In hippocampal slices maintained in vitro, 0.1 to 1.0 microM KA produced spontaneous epileptiform spikes, originating in CA3, and increased evoked potentials. Systemic KA is a potent means of inducing limbic seizures with a primary action in the hippocampus. We propose that this selective activation arises when KA augments excitatory glutamatergic synapses in critical epileptogenic areas, such as the CA3 region of the hippocampus.