The authors sought to investigate the role of a common single nucleotide polymorphism in the mu-opioid receptor gene (OPRM1) 118A > G for nociceptive sensory processing using event-related potentials (ERPs). Specific nociceptive (carbon dioxide [CO2]: 40% volume-to-volume [vol/vol] and 60% vol/vol) and nonnociceptive (hydrogen sulfide, 2 parts per million [ppm] and 4 ppm) stimuli were applied to the nasal mucosa of 45 volunteers. ERPs were recorded from a central lead. In this random sample, we found 37 noncarriers, 7 heterozygous carriers, and I homozygous carrier of the variant OPRM1 118G allele (allelic frequency, 10%). Amplitudes of nociceptive ERP in carriers of this allele were, on average, half as high as those of noncarriers. In discriminant analysis, ERP amplitude NI response to the weaker nociceptive stimuli was the only ERP parameter that discriminated statistically significantly between carriers and noncarriers of the variant 118G allele. On the basis of N1-CO2 (40% vol/vol), the authors correctly backclassified 68.6% of the cases as carriers or noncarriers of the allele. The OPRM1 118A > G polymorphism specifically modulates nociceptive but not nonnociceptive cortical activation.