Radiant laser pulses activate selectively skin nociceptors and elicit transient brain responses (laser-evoked potentials, LEPs). When LEPs are elicited by pairs of stimuli (S1-S2) delivered at different inter-stimulus intervals (ISIs), the S2-LEP is strongly reduced at short ISI (250 ms), and progressively recovers at longer ISIs (2000 ms). This finding has been interpreted in terms of order of arrival of nociceptive volleys and refractoriness of neural generators of LEP(Truini et al 2004, Garcia-Larrea 2004). However, an alternative explanation is the modulation of another experimental factor, the temporal expectancy of the eliciting stimulus (Mouraux and Iannetti 2008). To test this alternative hypothesis, we recorded LEPs elicited by pairs of nociceptive stimuli delivered at four ISIs(250-500-1000-2000 ms), using two different conditions. In the constant condition the ISI was identical across the trials of each block, while in the variable condition the ISI was varied randomly across trials, and single-stimulus trials were intermixed to paired trials. Therefore, S2s were much less expected in the variable than in the constant condition. In the constant condition there was a significant ISI-dependent suppression of the S2-LEP amplitude (p=0.0011, ANOVA; p=0.0006, post-test for linear trend). In contrast, in the variable condition the S2-LEP amplitude was completely unaltered (p =0.25, ANOVA). S2-LEP amplitudes were overall significantly reduced in the constant condition (p=0.0006, two-way ANOVA). These results indicate that the reduction of S2-LEP can be entirely explained by a modulation of temporal expectancy, and provide further support to the concept that the saliency of a sensory stimulus represents a crucial determinant of the magnitude of the elicited ERP response (Iannetti et al 2008, Mouraux and Iannetti 2009).