Abstract Two sequences of pervasive dolomitization are preserved in the Mississippian Burlington-Keokuk Formation of Iowa, Illinois, and Missouri. Cathodoluminescent petrography reveals (1) an early, post-depositional, dolomite-forming episode (dolomite I), and (2) a later dolomite (dolomite II), which replaced the first generation. These texturally and temporally distinct dolomites are correlative over 100,000 km 2 of outcrop and subsurface (see Cander and others, this volume) and have distinguishing isotopic and trace-element characteristics. Calculation of the simultaneous isotopic variations that occur during water-rock interaction demonstrates important differences in the relative rates at which the O, C., Sr, and Nd isotopic compositions of diagenetic carbonates are altered. These quantitative models are used to place constraints on the water-rock interaction history of the Burlington-Keokuk dolomites. Dolomite I samples have a range of δ 18 O (–2.2 to 2.5‰ PDB), δ 13 C (-0.9 to 4.0‰ PDB) and є Nd (342) values (–6.0 to –4.7), and initial 87 Sr/ 86 Sr ratios (0.70757 to 0.70808) that encompass estimated marine dolomite isotopic compositions. These samples also have 107 to 123 ppm Sr, slightly lower than that of modem marine dolomites. Dolomite I formed from predominantly seawater-derived constituents with a small but significant non-marine component. A mixed-marine meteoric-fluid model can quantitatively account for the variations in dolomite I isotope and trace-element compositions, but the origin of the non-marine component is not well constrained. Compared to dolomite I, dolomite II samples have radiogenic initial 87 Sr/ 86 Sr ratios (0.70885 to 0.70942), lower δ 18 O values (–6.6 to –0.2‰ PDB), depleted Sr concentrations (50 to 63 ppm), similar δ 13 C values (-1.0 to 4.1‰ PDB) and similar є Nd (342) values (–6.5 to –5). The isotopic composition and concentration of Sr in dolomite II preclude a source within the Burlington-Keokuk Formation for the Sr in dolomite II. Dolomite II apparently formed as a result of the recrystallization of the less stoichiometric dolomite I by extraformational subsurface fluids that migrated to shallow burial depths. The results suggest that the recrystallization process effectively exchanged nearly all of the Sr from dolomite I. Oxygen isotopes equilibrate between dolomite and fluid at relatively low extents of water-rock interaction, and as a result, the δ 18 O values of dolomite II may reflect only the last stages of recrystallization. The results of model calculations also suggest that the 87 Sr/ 86 Sr ratios of dolomite II preserve an earlier and larger record of water-rock interaction, whereas their C and Nd isotopic signatures are inherited from dolomite I precursors. Late-stage, vug-filling carbonates appear to have formed from extraformational fluids that experienced minimal interaction with Burlington-Keokuk host rocks. The petrology and geochemistry of Burlington-Keokuk dolomites document multiple episodes of pervasive water-rock interaction that can be correlated on a regionally extensive scale.