Radiolabeled probes for the transcription factor, activator protein-1 (AP-1), bound differentially to nuclear fractions of discrete structures of the guinea pig cochlea (organ of Corti, lateral wall tissues, and spiral ganglion). Noise exposure (4 kHz octave band, 115 dB, for 5 h) significantly increased AP-1 binding in both the organ of Corti and lateral wall tissues but not in the spiral ganglion. Supershift analysis using an antibody against c-Fos protein demonstrated that enhancement of AP-1/DNA binding was at least in part due to the expression of c-Fos protein. These results suggest that AP-1 is involved in the molecular mechanism(s) mediating noise-induced cochlear damage.