• In this study, we sought to determine the clinical usefulness of high-frequency audiometry (8000 to 20 000 Hz) in detecting aminoglycoside-induced increases in pure-tone hearing thresholds before they are noticed in conventionally tested frequencies. We measured hearing thresholds from 250 to 20 000 Hz in 22 patients with cystic fibrosis who were treated with aminoglycosides. The audiograms were age-matched and were compared with those from 13 patients with cystic fibrosis and 38 subjects without cystic fibrosis, all of whom had never received aminoglycoside therapy. In patients with cystic fibrosis who were treated with aminoglycoside (younger than 20 years), there were statistically significant elevations only in frequencies higher than 16000 Hz. Patients with cystic fibrosis who were treated with aminoglycosides who were 20 years and older had elevated thresholds in all frequencies tested. Patients with cystic fibrosis who were not treated with aminoglycosides did not differ statistically from controls. High-frequency audiometry may serve as a useful measure of elevation in pure-tone hearing thresholds that precede noticeable loss of auditory acuity in patients with cystic fibrosis who are receiving long-term aminoglycoside therapy.