The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.