Background The auditory steady state response (ASSR) is a sustained electrical response of the brain to auditory stimuli delivered at fast rates (30-50 responses/s). The aim of this study was to evaluate the effect of 0.26-0.50% isoflurane on the ASSR and on consciousness, defined as responsiveness to verbal commands. Methods: Ten volunteers (21-31 yr) participated. Isoflurane was administered at three stable, end-tidal concentrations: 0.26%, 0.38%, and 0.50%. The ASSR in response to 18,000 stimuli (500-Hz tonebursts, 10 ms, 82-dB, the right ear, 35-45 bursts/s) was recorded from the vertex with reference to the right mastoid. Recordings were made during baseline, at each isoflurane concentration, and during recovery. Results: The mean (SD) ASSR amplitudes were 0.32 (0.23) mu V during baseline, 0.24 (0.17) mu V during 0.26% isoflurane, 0.09 (0.05) mu V during 0.38% isoflurane, 0.04 (0.03) mu V during 0.50% isoflurane, and 0.29 (0.33) mu V during recovery. The amplitude during baseline and recovery was larger than during 0.38% and 0.50% isoflurane (P < 0.001). The amplitude at 0.26% was larger than at the other concentrations (P < 0.025). The logarithm of the ASSR amplitude was related linearly to the concentration of isoflurane (r = 0.85; P < 0.0001). The prediction probability (P-k) for loss of consciousness was 0.95 for both ASSR and measured isoflurane concentration. An ASSR amplitude < 0.07 mu V was always associated with unconsciousness. Conclusions The ASSR Is attenuated in a concentration-dependent manner by isoflurane. Suppression of consciousness and maximal attenuation of ASSR occur in the same isoflurane concentration range. Profound attenuation of ASSR appears to reflect unconsciousness, defined as unresponsiveness to verbal commands.