Bilingual individuals need effective mechanisms to prevent interference from one language while processing material in the other. Here we show, using event-related brain potentials and functional magnetic resonance imaging (fMRI), that words from the non-target language are rejected at an early stage before semantic analysis in bilinguals. Bilingual Spanish/Catalan and monolingual Spanish subjects were instructed to press a button when presented with words in one language, while ignoring words in the other language and pseudowords. The brain potentials of bilingual subjects in response to words of the non-target language were not sensitive to word frequency, indicating that the meaning of non-target words was not accessed in bilinguals. The fMRI activation patterns of bilinguals included a number of areas previously implicated in phonological and pseudoword processing, suggesting that bilinguals use an indirect phonological access route to the lexicon of the target language to avoid interference.