The genetic basis of organism response to stoichiometric mismatches between environmental availability and somatic demand is still poorly understood. This study reports a consistent genotype × environment interaction related to phosphorus : carbon availability to Daphnia. In multiple pairs of Daphnia pulicaria clones, genetic variation at the phosphoglucose isomerase (Pgi) locus indicated that Pgi-heterozygotes out competed Pgi-homozygotes under high P : C conditions, whereas the opposite outcome was observed under low P : C conditions. Estimates of phosphorus use efficiency indicated that homozygotes were significantly more efficient. However, homozygotes were comparatively less homeostatic. We hypothesize that lower specific activity of Pgi from homozygotes, which results in lowered energetic efficiency during the second glycolytic step, may underlie the competitive advantage enjoyed by homozygotes under low P : C (i.e. excess C) conditions. Our results show that analysing stoichiometric mismatches between diet and consumer should advance our quest for a fundamental understanding of the mechanisms driving genotype-environment interactions.