ABSTRACT: The distribution of the blue mussel Mytilus edulis spans a steep gradient of environmental stress between intertidal and subtidal habitats, and can provide insight into population-scale patterns and underlying processes of variation in physiological tolerances. I conducted a 7 wk reciprocal transplant of mussels between the upper intertidal and subtidal portion of their natural depth distribution, and then assayed their tolerance to either aerial exposure or submerged hypoxia in the laboratory. Intertidal mussels transplanted back to the intertidal had a tolerance to aerial exposure 50% higher than subtidal mussels that remained in the subtidal. That difference can be explained by changes in mussel physiology induced by ambient conditions, since the tolerance of mussels transplanted between the intertidal and subtidal became similar to mussels occurring naturally in each habitat. The tolerance of mussels to submergence in hypoxic water—an environmental stress exacerbated by anthropogenic factors that experimental mussels had not encountered in the field—followed a pattern qualitatively similar to the aerial exposure assay: intertidal mussels had higher survivorship in hypoxic water than those from the subtidal, and an elevated tolerance was induced by transplanting subtidal individuals to the intertidal. These results suggest that the response of mussels to a change in environmental conditions could vary between the center and edge of their depth distribution as a function of stress previously encountered.