Patients with unilateral, right frontal lobe damage (N = 13) and matched controls (N = 20) performed a task of lexical ambiguity resolution in order to explore the contribution of right frontal regions to lexical-semantic priming. Word triplets consisting of balanced homographs were presented to participants in four conditions: concordant, discordant, neutral, and unrelated. Controls demonstrated facilitation for concordant meanings of homographs, as evidenced by their faster reaction times in the concordant relative to the unrelated (baseline) condition, as well as a lack of facilitation for the discordant meaning relative to the neutral and concordant conditions. Results in patients with right frontal lobe damage differed depending on the site of the lesion. Patients with lesions restricted to the right medial frontal lobe only showed facilitation in the neutral condition, while those with lesions encroaching upon the right dorsolateral region demonstrated facilitation of both discordant and concordant meanings relative to the baseline condition. These results support a role for the right frontal lobe in semantic priming and suggest possible specialization within the right prefrontal cortex for the processing of lexical-semantic information. (JINS, 2005, 11, 132–143.)