The effects of three putative genes which contribute to age-related hearing loss (AHL genes) were evaluated using auditory brainstem response (ABR) thresholds and post-mortem cochlear histopathology in 25 recombinant BXD inbred mouse strains, originally derived from C57BL/6J (B6) and DBA/2J (D2) progenitor strains. All BXD strains showed substantial elevation of ABR thresholds and loss of spiral ganglion cells (SGCs) during the first year of life. The findings are consistent with our genetic model in which D2 and B6 inbred strains both possess the Ahl (age-related hearing loss) gene, whereas D2 possesses two additional chromosomal loci with AHL genes (Ahl2 and Ahl3). The between-strain distribution in the severity of SGC loss and ABR threshold elevations suggests that the severity of hearing loss is determined in large part by the number of AH L genes an animal possesses and by additional genetic background effects. The present findings also demonstrate that, because BXD strains vary substantially in the rate and severity of progressive hearing loss (but are genetically closely related), they can provide powerful animal models for developmental studies of AHL.