Electrophysiological correlates of the behaviorally well-documented inhibitory effect of first syllable-frequency during lexical access are presented. In a lexical decision task, response times to words with high-frequency first syllables were longer than those to words with low-frequency first syllables and resulted in more negative event-related potentials (ERPs) in an early time window from 190 ms to 280 ms and in the N400 component. The onset of the observed first syllable-frequency effect was prior to the onset of the effect of lexicality (i.e., the first reliable differentiation in ERP waveforms in response to words and pseudowords, a potential marker of lexical access). The present study's results support Barber et al.'s [Neuroreport 15 (2004) 545] notion of the prelexical nature of the first syllable-frequency effect by (A) providing evidence for electrophysiological correlates of first syllable-frequency in another, non-Romance orthography (i.e., German), (B) relating the onset of the first syllable-frequency effect to the onset of the lexicality effect and (C) strengthening this pattern of results by means of a novel item-based analysis of ERP data. Implications of the prelexical nature of the inhibitory first syllable-frequency effect for computational models of reading, specifically for Ans et al.'s [Psychol. Rev. 105 (1998) 678] multiple-trace memory (MTM) model of reading are discussed.