A better characterization of subsurface processes in hydrothermal systems is key to a deeper understanding of fluid-rock interaction and ore-forming mechanisms. Vent systems in oceanic crust close to subduction zones, like at Brothers volcano and in the eastern Manus basin, are known to be especially ore rich. We measured B concentrations and isotope ratios of unaltered and altered lava that were recovered from drilling sites at Brothers volcano and Snowcap (eastern Manus basin) to test their sensitivity for changing alteration conditions with depth. In addition, for Brothers volcano, quartz-water oxygen isotope thermometry was used to constrain variations in alteration temperature with depth. All altered rocks are depleted in B compared to unaltered rocks and point to interaction with a high-temperature (>150°C) hydrothermal fluid. The δ11B values of altered rocks are variable, from slightly lower to significantly higher than those of unaltered rocks. For Brothers volcano, at the Upper Cone, we suggest a gradual evolution from a fluid- to a more rock-dominated system with increasing depth. In contrast, the downhole variations of δ11B at Snowcap as well as δ11B and δ18O variations at the NW Caldera (Site U1530) of Brothers volcano are suggested to indicate changes in water-rock ratios and, in the latter case, also temperature, with depth due to permeability contrasts between different lithology and alteration type boundaries. Furthermore, δ11B values from the NW Caldera (Site U1527) might point to a structural impact on the fluid pathway. These differences in the subseafloor fluid flow regime, which ranges from more pervasive and fluid-controlled to stronger and controlled by lithological and structural features, have significant influence on alteration conditions and may also impact metal precipitation within the sea floor.