The Middle Devonian Marcellus Formation of North America is the most prolific hydrocarbon play in the Appalachian basin, the second largest producer of natural gas in the United States, and one of the most productive gas fields in the world. Regional differences in Marcellus fluid chemistry reflect variations in thermal maturity, migration, and hydrocarbon alteration. These differences define specific wet gas/condensate and dry gas production in the basin. Marcellus gases co-produced with condensate in southwest Pennsylvania and northwest West Virginia are mixtures of residual primary-associated gases generated in the late oil window and postmature secondary hydrocarbons generated from oil cracking in the wet gas window. Correlation of API gravity and C7 expulsion temperatures, high heptane and isoheptane ratios, and the gas geochemical data confirm that the Marcellus condensates formed through oil cracking. Respective low toluene/nC7 and high nC7/methylcyclohexane ratios indicate selective depletion of low-boiling point aromatics and cyclic light saturates in all samples, suggesting that water washing and gas stripping altered the fluids. These alterations may be related to deep migration of hot basinal brines. Dry Marcellus gases produced in northeast Pennsylvania and northcentral West Virginia are mixtures of overmature methane largely cracked from refractory kerogen and ethane and propane cracked from light oil and wet gas. Carbon and hydrogen isotope distributions are interpreted to indicate (1) mixing of hydrocarbons of different thermal maturities, (2) high temperature Rayleigh fractionation of wet gas during redox reactions with transition metals and formation water, (3) isotope exchange between methane and water, and, possibly, (4) thermodynamic equilibrium conditions within the reservoirs. Evidence for thermodynamic equilibrium in the dry gases includes measured molecular proportions (C1/(C1 − C5) = 0.96 to 0.985) and δ13C1 values significantly greater than δ13CKEROGEN. Noble gas systematics support the interpretation of hydrocarbon–formation water interactions, constrain the high thermal maturity of the hydrocarbon fluids, and provide a method of quantifying gas retention versus expulsion in the reservoirs.