Acute changes in the electrophysiology and ultrastructure of the organ of Corti were studied after microperfusion of c. 5 × 10⁶ CFU of serotype 2 Streptococcus pneumoniae D39 or Escherichia coli K-12 directly into the scala tympani of guinea pigs. Hearing loss was assessed by recording the auditory nerve compound action potential response to a 10 kHz tone pip. Mean hearing loss 3 h after pneumococcal perfusion (n=4) was 44 dB, compared to 6 dB after E. coli perfusion (n=4) (P<0.001). After pneumococcal perfusion, scanning electron microscopy revealed damage to hair cell stereocilia and cratering of the apical surface of supporting cells. Intraperitoneal injection of l00 mg/kg cefotaxime (n=4) or l00 mg/kg amoxycillin (n=4) 30 min before perfusion of pneumococci significantly reduced mean hearing loss to 23 dB (P=0.01) or 20 dB (P=0.01), respectively, and diminished ultrastructural damage. The data suggest that if pneumococci invade the inner ear during meningitis, cochlear deafness may rapidly ensue.