The chemistry of water in the Cambrian-Ordovician aquifer in six midwestern states has been studied as part of the Northern Midwest Regional Aquifer-System Analysis of the U.S. Geological Survey. Dissolved-solids concentrations generally increase perpendicular to the direction of regional groundwater flow, from less than 400 mg/liter in southeast Minnesota, southwest Wisconsin, and northeast Iowa to more than 10,000 mg/liter in northwest Missouri. Isotopic ratios of hydrogen and oxygen are significantly depleted from north to south, with an areal distribution approximately parallel to the distribution of dissolved solids. For example, ??18O in southern Iowa and northern Missouri is about 6 parts per thousand lighter than ??18O of modern recharge water in Minnesota and Wisconsin. Covariance between ??18O and ??D of the groundwater, similar to that of modern precipitation, suggests that the differences in isotopic ratios between groundwater and modern recharge water reflect meteoric signatures of water during past recharge events rather than geochemical processes such as isotopic exchange with aquifer materials. The pronounced parallelism between the distribution of isotopes and dissolved solids over large areas probably reflects largescale recharge of Pleistocene glacial meltwater into the aquifer system, which probably had a paleoflow system with a gradient from northeast to southwest rather than from northwest to southeast. ?? 1984.