A suite of middle Miocene Deep Sea Drilling Project sites in the southwest Pacific reveals large-scale changes in deepwater circulation associated with East Antarctic Ice Sheet (EAIS) variations from ∼16.5 to 13.8 Ma. Oxygen and carbon isotopic records based on Cibicidoides benthic foraminifera from a depth transect (sites 590B, 588A, 591B, and 206 from 1200- to 3150-m paleodepth at ∼35°S paleolatitude) and from a meridional transect (sites 588A, 590B, 593, and 594 from 30° to 48°S paleolatitude at intermediate water depth) allow detailed examination of southwest Pacific deepwater circulation from ∼17.5 to 12 Ma. Significantly, intervals of low δ18O from 16.5 to 16.3 Ma and perhaps at 15.7 Ma were marked by similar δ18O values at upper bathyal (∼1200–1500 m; sites 588A and 590B) and midbathyal (∼2100 m; site 591B) water depths. Small vertical δ18O gradients during δ18O minima may indicate warm saline deep water (WSDW) at midbathyal depths in the southwest Pacific during intervals of inferred global warmth and low global ice volume. Increased vertical δ18O gradients after ∼15.6 Ma and especially after 13.8 Ma indicate increased production of Southern Component Water (SCW) in association with EAIS growth. These data are consistent with the hypothesis (Woodruff and Savin, 1989) that major EAIS growth was fostered by diminished meridional heat transport to the high southern latitudes related to the termination of Tethyan Indian Saline Water (TISW) and an increase in SCW production during the early middle Miocene after ∼15.6 Ma. Further, a maximum vertical carbon isotopic gradient of ∼0.8 ‰ at 13.6 Ma suggests that Southern Component Intermediate Water (SCIW) production and Pacific Deep Water (PDW) strength were each at a maximum at this time and were critical to major EAIS growth. The establishment of near-modern δ13C and δ18O gradients following major EAIS growth from ∼14.0 to 13.8 Ma marks a major step in the development of the Neogene ocean/cryosphere system.