The zebra mussel, Dreissena polymorpha, is widespread in the St. Lawrence River while the conspecific quagga mussel, Dreissena bugensis, is found only in the Lake Ontario outflow region of the river. This situation provided an opportunity to evaluate in situ environmental and interspecific heterogeneity in shell and tissue growth. Shell dry weight, carbon content, and shell strength of D. polymorpha from the four spatially discrete water masses differed significantly. For instance, D. polymorpha total and tissue mass increased over the summer in the shallow fluvial Lac Saint-Pierre but decreased in the upstream and downstream water masses. Standardized shell mass and strength of D. polymorpha was lowest where the mussels experienced salinity or low calcium. Although the response pattern of mass and glycogen content for D. polymorpha was spatially complex, mussels from the stressful oligohaline estuary population had the weakest shells and lowest glycogen content, even though their standardized tissue mass was the heaviest. This disparity in shell and tissue response suggests that some aspect of shell physiology alone may be limiting these mussels in estuarine environments. Tissue characteristics of D. polymorpha and D. bugensis were similar at the site where both were present, but the shell strength of D. bugensis was only equivalent to the weakest of D. polymorpha. We also conclude that lighter shells might make D. bugensis more susceptible to predation or mechanical damage but may also offer a bioenergetic advantage that is contributing to its rapid displacement of D. polymorpha where the two species co-occur.