The role of substantia nigra (SN) in the development of kindling was investigated. Microinjection of gamma-vinyl gamma-aminobutyric acid (GVG), a gamma-aminobutyric acid (GABA) transaminase inhibitor, into the SN bilaterally retarded kindling development by 77%. GVG injected dorsal to the SN did not alter the kindling rate. By contrast, lesions of the SN, whether by thermocoagulation or by microinjected neurotoxin, N-methyl-D,L-aspartate, facilitated kindling development by 27-44%. Thermocoagulative lesions dorsal to the SN did not affect the rate of kindling development. Thus these two manipulations, each presumed to suppress the activity of the SN, resulted in opposite effects on kindling development. We interpret the pharmacologic findings to indicate that the intact SN can powerfully facilitate kindling development. However, the SN is not vital for kindling development, since kindling can be established after destruction of a considerable portion of SN. Whether the increased rate of kindling development following SN lesions is due solely to the absence of SN remains unclear.