Effects of arginine-vasopressin (AVP) on the habituation of the orienting reaction and response to stimulus mismatch were investigated in a between-group design with 40 healthy male volunteers using skin conductance and heart rate responses as dependent measures. Twenty-one 1000 Hz tones of 90 dB(A) intensity and 2 s duration were presented with alternating intervals of 20 and 140 s. Stimulus mismatch responses were analyzed to the tones after the long intervals and to a change of the interval duration. The expected prevention of habituation as an indicator of a general stimulus-related increase of phasic arousal under AVP could not be confirmed. There were no differences between the AVP and the placebo group in the skin conductance and heart rate responses. The interval change did not provoke a dishabituation reaction, but responses to the tones after the long intervals were reliably enhanced. However, AVP did not increase the reaction to stimulus mismatch. It is concluded that autonomic indicators of the habituation of the OR remain unaffected by AVP.