Wide-angle reflections generated by five controlled blasts and over 110 timed quarry blasts in the Southern Appalachians were used to test models for isostatic compensation of topography. The profiles cross the Appalachian gravity gradient and gravity low and sample the highest elevations within the orogen. Migration of P, SV, and SH reflections suggests that crustal thickness varies from 35 to 39 km within the coastal plain and 37–39 km within the Carolina terrane. It increases northwestward from 40 to 45 km across the Inner Piedmont, and then thickens to 50–52 km along the southeastern flank of the Blue Ridge Mountains. Crustal thickness within the Blue Ridge Mountains ranges from 47 to 56 km. Receiver functions for broadband stations GOGA and MYNC show a similar pattern in crustal thickness. Assuming Airy compensation, the correlation between elevation and Moho depth suggests a range of 50–150 kg/m3 for the density contrast between the crustal root and mantle. The greatest Moho depths are associated not with the tallest peaks, but rather with the broadest portions of the mountain chain. This observation is consistent with regional bending of the lithosphere. However, the planar basement surface suggests that the root either predates Alleghanian thrusting, and therefore is unrelated to the present topography, or formed in response to some other mechanism. Bounds on curvature of the basement surface suggest a lower bound of 30–40 km for the effective elastic thickness of the lithosphere. This is consistent with previous estimates for the southern Appalachians based on analysis of gravity data.