To determine whether participants with normal visual acuity, no ophthalmoscopically signs of age-related maculopathy (ARM) in both eyes, and who are carriers of the CFH, LOC387715, and HRTA1 high-risk genotypes (gene-positive) have impaired rod- and cone-mediated mesopic visual function compared with persons who do not carry the risk genotypes (gene-negative).Fifty-three Caucasian study participants (mean 55.8 ± 6.1) were genotyped for CFH, LOC387715/ARMS2, and HRTA1 polymorphisms. Single-nucleotide polymorphisms were genotyped in the CFH (rs380390), LOC387715/ARMS2 (rs10490924), and HTRA1 (rs11200638) genes using optimized gene-expression assays. The critical fusion frequency (CFF) mediated by cones alone (long-, middle-, and short-wavelength sensitive cones, LMS) and by the combined activities of cones and rods (LMSR) were determined. The stimuli were generated using a four-primary photostimulator that provides independent control of the photoreceptor excitation under mesopic light levels. Visual function was further assessed using standard clinical tests, flicker perimetry, and microperimetry.The mesopic CFF mediated by rods and cones (LMSR) was significantly reduced in gene-positive compared to gene-negative participants after correction for age (P = 0.03). Cone-mediated CFF (LMS) was not significantly different between gene-positive and -negative participants. There were no significant associations between flicker perimetry and microperimetry and genotype.This is the first study to relate ARM risk genotypes with mesopic visual function in clinically normal persons. These preliminary results could become of clinical importance because mesopic vision may be used as a biomarker to document subclinical retinal changes in persons with risk genotypes and to determine whether those persons progress into manifest disease.