Four experiments were designed to investigate whether the frequency of words used to create pseudowords plays an important role in lexical decision. Computational models of the lexical decision task (e.g., the dual route cascaded model and the multiple read-out model) predict that latencies to low-frequency pseudowords should be faster than latencies to high-frequency pseudowords. Consistent with this prediction, results showed that when the pseudowords were created by replacing one internal letter of the base word (Experiments 1 and 3), high-frequency pseudowords yielded slower latencies than low-frequency pseudowords. However, this effect occurred only in the leading edge of the response time (RT) distributions. When the pseudowords were created by transposing two adjacent internal letters (Experiment 2), high-frequency pseudowords produced slower latencies in the leading edge and in the bulk of the RT distributions. These results suggest that transposed-letter pseudowords may be more similar to their base words than replacement-letter pseudowords. Finally, when participants performed a go/no-go lexical decision task with one-letter different pseudowords (Experiment 4), high-frequency pseudowords yielded substantially faster latencies than low-frequency pseudowords, which suggests that the lexical entries of high-frequency words can be verified earlier than the lexical entries of low-frequency words. The implications of these results for models of word recognition and lexical decision are discussed.