This paper describes the chemical composition and relative deuterium concentration of primary fluid inclusions in ore and gangue minerals from the Cave-in-Rock and Upper Mississippi Valley districts - both of which are of the Mississippi Valley type. Compositional changes are compared to the paragenetic sequence. The fluid inclusions in the early ore minerals are nearly saturated sodium-calcium chloride brines. Fluid inclusions in late minerals are less concentrated and have a lower relative deuterium concentration. In the Cave-in-Rock district the composition of primary fluid inclusions in yellow fluorite, the earliest ore mineral, is similar to that of connate water in the Illinois basin in the same strata as the ore deposits. The change in composition of fluid inclusions in the later quartz and sulfide minerals indicates a water of different origin, possibly magmatic, was introduced. Connate and possible magmatic waters were largely flushed out during deposition of the gangue minerals in the last stages of mineralization, and the composition of the fluid inclusions in these gangue minerals trends toward that of meteoric water or a dilute mixture of meteoric and magmatic water. In the Wisconsin-Illinois-Iowa district, fluid inclusions in the ore minerals are highly concentrated sodium-calcium chloride brines that have a high relative deuterium concentration; inclusion fluid in late gangue minerals contains less deuterium and is relatively dilute.