Low-frequency irregular words are named more slowly and are more error prone than low-frequency regular words (the regularity effect). Rastle and Coltheart (1999) reported that this irregularity cost is modulated by the serial position of the irregular grapheme-phoneme correspondence, such that words with early irregularities exhibit a larger cost than words with late ones. They argued that these data implicate rule-based serial processing, and they also reported a successful simulation with a model that has a rule-based serial component—the DRC model of reading aloud (Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001). However, Zorzi (2000) also simulated these data with a model that operates solely in parallel. Furthermore, Kwantes and Mewhort (1999) simulated these data with a serial processing model that has no rules for converting orthography to phonology. The human data reported by Rastle and Coltheart therefore neither require a serial processing account, nor successfully discriminate among a number of computational models of reading aloud. New data are presented wherein an interaction between the effects of regularity and serial position of irregularity is again reported for human readers. The DRC model simulated this interaction; no other implemented computational model does so. The present results are thus consistent with rule-based serial processing in reading aloud.