Slices of olfactory cortex from guinea pig, incorporating the lateral olfactory tract (LOT), were maintained in a glucose-bicarbonate solution in vitro. Stimulation of the LOT produced: 1) A summed LOT action potential; 2) A monosynaptic surface-negative wave (N-wave); and 3) A polysynaptic surface-positive wave (P-wave) as recorded from the pial surface of the slice at 24 degrees C. During a period of single stimulus pulses to the LOT, local anesthetics and barbiturates, applied to the incubating solution, depressed the amplitude of the action potential (while increasing its latency and threshold) with the following potencies: tetracaine greater than cocaine greater than lidocaine greater than procaine greater than pentobarbital greater than phenobarbital. The order of potencies was similar for the synaptic potentials. Each local anesthetic or bartiturate first depressed the P-wave, the N-wave and then the LOT potential, with all three potentials being affected within a narrow range of drug concentrations. There was a good linear relationship between drug potency on all potentials and the distribution coefficients of the drugs in octanol-water. During a period of double stimulus pulses to the LOT, up to 10 seconds apart, low concentrations of barbiturates depressed the N-wave to the second pulse with little effect on the first, conditioning pulse, an effect not seen with local anesthetics. The bath concentrations required for this effect of both barbiturates were similar to previous reports of blood concentrations required for general anesthesia. It appears that local anesthetics have actions on brain similar to those reported for other tissues and that barbiturates share some of the actions of local anesthetics, but exert a selective depression on repetitively elicited synaptic potentials.