Epidosites are a prominent type of subseafloor hydrothermal alteration of basalts in ophiolites and Archean greenstone belts, showing an end-member mineral assemblage of epidote + quartz + titanite + Fe-oxide. Epidosites are known to form within crustal-scale upflow zones and their fluids have been proposed to be deep equivalents of ore-forming, black-smoker seafloor vent fluids. Proposals for the mass of fluid per mass of rock (W/R ratio) needed to form epidosites are contradictory, varying from 20 (Sr isotopes) to > 1000 (Mg mobility). To test these proposals we have conducted a petrographic, geochemical and reactive-transport numerical simulation study of the chemical reaction that generates km3-size epidosite zones within the lavas and sheeted dike complex of the Semail ophiolite, Oman. At 250–400 °C the modelled epidosite-forming fluid has near-neutral pH, it is highly oxidized and has low S and extremely low Fe contents. These features argue against the proposal that epidosite fluids are equivalents of black-smoker fluids. The Semail epidosites formed by replacement of lavas already altered to albite–chlorite–actinolite (spilite) assemblages, with the rare end-member epidosites requiring enormous W/R ratios of 700 to ~40000, depending on initial Mg content and temperature. Thus, the variably altered Semail epidosite zones record flow of ~1015 kg of fluid through each km3 of precursor spilite rock. This fluid imposed on the epidosite an Sr-isotope signature inherited from the previous rock-buffered chemical evolution of the fluid through the oceanic crust, thereby explaining the apparently contradictory low W/R ratios based on Sr isotopes.