Over the last century, sea level change has been considered one of the more plausible mechanisms of extinction in the marine realm (Chamberlin, 1898a(Chamberlin, , 1898bMoore, 1954;Newell, 1967;Johnson, 1974;Hallam, 1989). However, the processes that link sea-level change with extinction remain poorly understood (Valentine and Jablonski, 1991). The biotic effects of sea-level change are difficult to determine because of a tendency toward poor preservation of true stratigraphic ranges near extinction horizons caused by (1) facies shifts during relative sea-level rises and falls, and (2) erosion during lowstands, which destroys much of the evidence necessary to link sea-level change with a specific cause of extinction. Furthermore, the lack of extinctions during ABSTRACT Sequence stratigraphy provides a paleoenvironmental and chronostratigraphic framework within which to study long-term lithologic and biotic change. Observing the occurrence of taxa through several stratigraphic sequences can distinguish faunal tracking, the disappearance of taxa due to shifting lithofacies within a sequence, from regional extirpation, the elimination of taxa from a significant geographic area for at least one stratigraphic sequence. Sequence analysis of Mohawkian and Cincinnatian strata in the eastern United States reveals regional extirpations among articulate brachiopods and tabulate and rugose corals. These extirpations occurred in response to eustatic sea-level changes and the effects of the Taconic orogeny, which increased turbidity and nutrient input, decreased water temperature, and inhibited carbonate production across eastern North America. The timing of extirpations varied geographically and occurred first in the southern Appalachians (middle Mohawkian), next in the northern Appalachians (late Mohawkian), and last on the Cincinnati Arch (late Mohawkian to early Cincinnatian). The specific cause of the extirpations is still unknown; however, the timing of the extirpations appears to correlate with pulses of siliciclastic muds that were introduced during transgressive systems tracts. Several genera that were extirpated regionally returned to the eastern United States in the late Cincinnatian (Richmondian) along with an influx of several new genera. This invasion appears to be timed with the return of tropical carbonates to this portion of the United States. Sequence analysis of long-term lithologic and biotic change can help constrain the timing and cause of biotic events in the fossil record and thus can lead to an increased understanding of long-term ecologic and evolutionary processes.