Some of the most intense neotectonic activity known in the continental interior of North America has been recently discovered on a fault zone in the Thebes Gap area, Missouri and Illinois. This faulting almost assuredly was accompanied by large earthquakes. The zone is located approximately 30 km north of the New Madrid seismic zone and consists of complex north-northeast- to northeast-striking, steeply dipping faults that have had a long-lived history of reactivation throughout most of the Phanerozoic. Geophysical studies by others suggest that the faults are rooted in the deeply buried Late Proterozoic and Early Cambrian Reelfoot rift system. Quaternary deposits are cut by at least four episodes of faulting, two of which occurred during the Holocene. The overall style of neotectonic deformation is interpreted as right-lateral strike-slip faulting. At many locations, however, near-surface displacements have stepped from one fault strand to another and produced normal and oblique-slip faults in areas of transtension and high-angle reverse faults, thrust faults, and folds in areas of transpression. There is evidence of reactivation of some near-surface fault segments during the great 1811-1812 New Madrid earthquakes. Quaternary faulting at Thebes Gap demonstrates that there are additional seismic-source zones in the Midcontinent, U.S., other than New Madrid, and that even in the absence of plate-margin orogenesis, intense neotectonic activity does occur over long time periods along crustal weakenesses in continental interiors.