A tropical Pacific climate state resembling that of a permanent El Niño is hypothesized to have ended as a result of a reorganization of the ocean heat budget approximately 3 million years ago, a time when large ice sheets appeared in the high latitudes of the Northern Hemisphere. We report a high-resolution alkenone reconstruction of conditions in the heart of the eastern equatorial Pacific (EEP) cold tongue that reflects the combined influences of changes in the equatorial thermocline, the properties of the thermocline's source waters, atmospheric greenhouse gas content, and orbital variations on sea surface temperature (SST) and biological productivity over the past 5 million years. Our data indicate that the intensification of Northern Hemisphere glaciation approximately 3 million years ago did not interrupt an almost monotonic cooling of the EEP during the Plio-Pleistocene. SST and productivity in the eastern tropical Pacific varied in phase with global ice volume changes at a dominant 41,000-year (obliquity) frequency throughout this time. Changes in the Southern Hemisphere most likely modulated most of the changes observed.