Comparisons of carbon isotopic data on benthic foraminifera from Deep Sea Drilling Project sites 502 (western Caribbean) and 503 (eastern Pacific) indicate that the difference between the Atlantic and the Pacific in the per mil enrichment in carbon-13 of total dissolved carbon dioxide increased about 6 million years ago and again 3 million years ago, when the difference reached the modern level (1 per mil). Comparisons of planktonic foraminiferal oxygen isotopic data for the Caribbean and the Pacific suggest that the salinity of Caribbean surface waters began increasing 4 million years ago, possibly in response to shoaling of the Panama isthmus. These results suggest that modern circulation patterns in the Caribbean and eastern Pacific developed by 3 million years ago in concert with changing tectonic, climatic, and biogeographic patterns.