Marine climatic and sea-level changes in the eastern United States show two distinct modes: a gradual, directional Pliocene warming that ended with an abrupt regression, and a quasi-cyclic, high-amplitude, high-frequency middle-late Pleistocene pattern of alternating glacials and interglacials. Pliocene marine sediments of the Duplin Formation, deposited during a period of high sea level between 4.0 and 2.8 Ma BP, contain increasing percentages of tropical and subtropical ostracods, signifying a gradual warming. After maximum warm-water temperatures ca. 3.2-2.8 Ma BP, sea level dropped; this was followed by extensive subaerial erosion between about 2.8 and 2.0 Ma BP. This series of events reflects the emergence of the Isthmus of Panama between about 3.5 and 3.0 Ma BP, concomitant intensification of warm Gulf Stream flow along the eastern U.S.A., and initial Pliocene glaciation in the Northern Hemisphere. In the middle-late Pleistocene, glacial-interglacial cycles occurred with a periodicity of ca. 100 ka. Four (possibly five) emerged interglacial marine sequences correlate with deep-sea oxygen-isotope stages 13/11, 7, 5, and 1. During some interglacials, however, climatic conditions ranged from full interglacial warmth to cool, nearly interstadial conditions; this observation indicates short-term regional climatic variability.