Joke comprehension deficits in patients with right hemisphere (RH) damage raise the question of the role of the intact RH in understanding jokes. One suggestion is that semantic, or meaning, activations are different in the RH and LH, and RH meanings are particularly important for joke comprehension. To assess whether hypothesized differences in semantic activation in the two hemispheres were relevant to joke comprehension, we recorded event-related brain potentials (ERPs) as healthy adults read laterally presented “punch words” to one-line jokes and nonjoke controls. Jokes presented to the RVF/LH elicited larger amplitude N400 than the nonjoke endings; when presented to the LVF/RH, the joke and nonjoke endings elicited N400s of equal amplitude. This finding suggests that semantic activations in the two hemispheres do differ, with RH semantic activation facilitating joke comprehension.