To address the impact of differences in language lateralization on joke comprehension, event-related brain potentials (ERPs) were recorded as 16 left- and 16 right-handed adults read one-line jokes and non-funny control stimuli ("A replacement player hit a home run with my girl/ball,"). In right-handers, jokes elicited a late positivity 500-900 ms post-stimulus onset that was largest over right hemisphere (RH) centro-parietal electrode sites, and a slow sustained negativity over anterior left lateral sites. In left-handers, jokes elicited a late positivity 500-900 ms post-onset that was larger and more broadly distributed than in the right-handers' ERPs. In right-handed women, the late positivity was larger over RH electrode sites. In left-handed women, the late positivity was bilaterally symmetric. The highly asymmetric slow sustained negativity over left anterior electrode sites was absent from left-handers' ERPs to jokes. Differences may reflect more efficient inter-hemispheric communication in the left-handers, as they are reputed to have relatively larger corpus callosal areas than right-handers. Results support the portrait of more bilateral language representation among left-handers, and suggest language lateralization affects high-level language comprehension tasks such as joke comprehension.