The effect of restraint stress via immobilization on rat cochlear glucocorticoid receptor (GR) levels was determined using an enzyme-linked immunosorbent assay (ELISA). Results demonstrated that GR levels in cochlear tissues exhibited tissue-specific and time-dependent responses to immobilization (6 hours daily). Similar responses of the GR were observed in rats restrained during two different times of the day. A significant quadratic trend (P = 0.019, R2 = 0.58) was observed in levels of GR in spiral ligament tissues of rats restrained from 10:00 to 16:00 h; levels of GR were elevated by day 2, and by day 21 GR levels had returned to near normal levels. GR levels in the spiral ligament tissues also were found to increase significantly after 2 days in response to repeated restraint stress administered from 06:00 to 12:00 h (P = 0.017, R2 = 0.34). Interestingly, a subtle, but statistically significant, decreasing trend in the organ of Corti's GR levels was detected when the daily restraint stress was applied from 06:00 to 12:00 h for up to 7 days. No significant trends (P > 0.05) were observed in GR levels of stria vascularis tissues regardless of the time of the restraint protocol. Stress has been implicated as an etiological factor in Ménière's disease and other ear pathologies. The data presented here indicate that the effect of stress is specific to tissue region and that, as in tissues of other systems, the GR of cochlear tissues are responsive to stress. © 1995.