The alterations in environmental parameters anticipated during global climate change are predicted to intensify physiological stress to marine ectotherms and impose selective regimes on their stress-tolerance capacities. The limits to which the effects on ecosystems will be buffered by phenotypic plasticity and adaptation of populations appear unpre- dictable. One of the most universal reactions to environmental stress is the classic heat shock response, and its evaluation in intertidal invertebrates, which experience extreme fluctuations in stress levels, may be useful to advance in the mechanistic understanding of future regime shifts. Using real-time RT-qPCR, I quantified the heat shock response in limpets of the genus Nacella that had been subjected to tidal emersion under natural conditions in field experiments at two locations in Chile. In a subpolar limpet population from Punta Arenas in the Strait of Magellan, high-intertidal limpets showed delayed stress responses, including markedly lower expression of the hsp70A gene, in comparison to their subtidal congeners. Low-intertidal limpets from a warmer acclimatized population sampled at Puerto Montt (Central Chile) exhibited the highest stress response to tidal emersion, presumably due to higher temperatures affecting air exposed animals in a cold-temperate as compared to a subpolar environment. On the genomic level, the subtidal and intertidal subpopulations display a conspicuous divergence in two distinct hsp70A allele groups, as evidenced by a discrepancy in F’st estimates in comparison to neutral genetic markers. My work indicates that Patagonian limpets show a graded heat shock response, increasing from South to North on a latitudinal gradient and from low to high on a tidal stress gradient. It provides indication for adaptive divergence of the hsp70A gene in these South American limpets, which might be explained by the selective effect of environmental stress caused by tidal emersion. Furthermore, it illustrates the great explanatory potential, but also conceptual difficulties of the heat shock response as an integrative biomarker for environmental stress. Stability assessment of reference genes is an integral part of quantification of the response, as stress conditions can cause down-regulation of constitutive genes and lead to overestimation of stress response levels. The quantification of response levels has to be performed against a thoroughly assessed background of inter-individual variation, population dynamic history and potential sequence adaptation.