Although the P300 event-related potential (ERP) is the most likely central measure of Sokolov's Orienting Reflex (OR), there are few systematic comparisons with the skin conductance response (SCR), the "gold standard" electrodermal OR measure. We examine habituation, stimulus significance, and inter-stimulus interval (ISI) effects in SCRs and components of the P300 from single-trial ERPs in an auditory dishabituation paradigm. Single trial ERP components were separated by temporal principal components analysis, and five components of the P300 were examined as potential phasic OR measures: P3a, P3b, Novelty P3, and two Slow Waves (SW1, SW2). Across the factors of ISI and significance, SCRs showed decrement over trials, recovery at a deviant, and dishabituation at the subsequent standard. This general pattern was not present in any of the components of the P300. SCRs were also larger to significant stimuli and at the long ISI; effects differed between P300 components. The electrodermal SCR showed the complete profile over trials expected of the phasic OR, and was enhanced by stimulus significance, confirming it as the model measure of Sokolov's phasic OR. Components of the P300 failed to match this profile, but instead appear to reflect different aspects of the stimulus processing involved in OR elicitation.