BACKGROUND: Essential hypertension results from the interaction of several genetic and environmental factors. Identification of genetic factors that modulate blood pressure (BP) response to interventions can lead to improved strategies for prevention and control. The purpose of this study was to identify genes that modulate BP response to dietary interventions. METHODS: We used data and samples collected in two randomized feeding studies to determine the extent to which genetic architecture is associated with the effect on BP of sodium intake and the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. Participants in both trials were adults with above-optimal BP or unmedicated stage 1 hypertension. Genomic DNA was typed for several candidate genes. RESULTS: The effect of sodium intake on BP differed by genotype at the angiotensinogen, β2-adrenergic receptor, and kallikrein loci. The effect of DASH dietary pattern on BP differed by genotype at the β2-adrenergic receptor locus. CONCLUSIONS: These findings have implications for understanding the mechanism(s) through which diet affects BP, the heterogeneity of these effects, and the extent to which dietary interventions can modulate genetic predisposition.