Recent investigations in a variety of experimental animal models suggest a close relationship between brain catecholamine and epileptic seizures. The aim of this study was to clarify the role of catecholamines in the epileptogenic focus. Thirty-eight adult cats were used for the experiments. After anesthetized by intraperitoneal injection of pentobarbital, cats were placed in stereotaxic apparatus and the bilateral parietal cortices were exposed. The electrocorticogram was recorded with two pairs of cotton-tipped electrodes applied on the pia. An epileptogenic focus was produced by intracortical injection of penicillin G in left middle suprasylvian gyrus. The sham-operation was done in the right cortex. At four different stages of development and propagation of penicillin spikes, bilateral cerebral cortices were excised and rapidly frozen in liquid nitrogen. Four stages of penicillin spikes were classified as follows: Stage 0: Spikes do not yet appear after penicillin injection. Stage 1: Spikes localize only in focal cortex. Stage 2: Spikes slightly propagate to non-focal cortex. Stage 3: Spikes fully propagate to non-focal cortex. Catecholamine analysed by gas chromatography with electron capture detector. In control cats, injected saline solution in bilateral cerebral cortices, the levels of dopamine and norepinephrine were 47±7 ng/g and 26±2 ng/g, respectively. Dopamine contents in focal cortex were significantly reduced in Stage 0 and increased conversely in Stage 3 compared with the control values. In non-focal cortex, dopamine contents significantly increased in Stages 1 to 3. Norepinephrine contents in both focal and non-focal cortex showed the same changes as dopamine. On the other hand, the contents of dopamine and norepinephrine showed the significantly lower levels in focal cortex compared with those in non-focal cortex in Stages 1 and 2. In Stage 3, however, there was no difference of catecholamine levels between focal and non-focal cortex. Octopamine, which is recently supposed as neurotransmitter substance in central nervous system, was detected in significantly high levels in focal cortex of Stage 1. From the results of this experiment and our previous studies, it is suggested that catecholamine, especially dopamine, play an important role in development of penicillin-induced epileptic focus in the cerebral cortex. Based on the results of this study, a relationship between epilepsy and brain catecholamines was discussed.