The June 10, 1987 southeastern Illinois earthquake (mb =5.0) is the largest event to have taken place in the northern midcontinent for 19 years, and is one of only seven events of comparable size to have occurred in this area in the 200-year historical record. The earthquake occurred near a transition zone between the northeast-trending Wabash Valley Fault System and the northwest-trending La Salle flexural belt. The main shock epicenter is positioned 30 km north of the northernmost mapped Wabash Valley faults, and detailed structural mapping in this area documents a systematic decrease in displacement along these faults approaching this termination. Immediately to the northeast of the main shock begins a major northwest-trending late Paleozoic fold structure: the La Salle Anticlinal Belt. This structural feature, marking a major flanking monocline of the Illinois Basin, displays over 750 meters of relief disrupting the lower Paleozoic strata, as well as the Precambrian basement surface. While there is little indication of faulting of the uppermost Paleozoic strata, the sharpness of the relief on the basement and limited seismic reflection data suggest that high-angle basement faulting, down-dropped toward the basin, has occurred beneath the Paleozoic cover. The transition between these two structural regimes may be accompanied by a sharp change in the regional contemporary stress orientation, from east-west compression in northern and central Indiana to north-northeast-trending compression in the Wabash and Ohio River valleys. The earthquake focal mechanism, like that of two other events in the area, indicates a nearly east-west P-axis, paralleling the trend of other contemporary stress indicators. Well constrained depths of aftershocks suggest that the main shock occurred at a depth of 7–11 km, which would place it within the mid-crust, 4–6 km below the top of the Precambrian basement. We propose that the southeastern Illinois event is associated with basement deformation within a complex structural transition zone connecting the two tectonic regimes, rather than the result of reactivation of a simple graben-like extension of the New Madrid Seismic Zone.