It is usually assumed that lexical representations are abstract and devoid of detailed information about various sources of acoustic variability. This assumption is evaluated in this study by examining the effect of talker variability on the access to word meaning in a short-term semantic priming experiment. Prime–target pairs that were semantically related (e.g., king–queen) or unrelated (e.g., bell–queen) were produced by the same talker or different talkers. Two inter-stimulus intervals (50 ms and 250 ms) were used between the prime and target to explore the time course of semantic priming. The auditory stimuli were presented to 60 college-age listeners, who performed lexical decision tasks. It was hypothesized that a change in the talker between the prime and target would influence the magnitude of semantic facilitation. Analysis of response accuracy and reaction time showed that the magnitude of semantic priming was attenuated in the different-talker condition, although the effect was obtained only for targets produced by the female speaker. There were no effects involving different inter-stimulus intervals. These results provided partial evidence that talker variability affects lexical access.