Can neural responses of a small group of individuals predict the behavior of large-scale populations? In this investigation, brain activations were recorded while smokers viewed three different television campaigns promoting the National Cancer Institute’s telephone hotline to help smokers quit (1-800-QUIT-NOW). The smokers also provided self-report predictions of the campaigns’ relative effectiveness. Population measures of the success of each campaign were computed by comparing call volume to 1-800-QUIT-NOW in the month before and the month after the launch of each campaign. This approach allowed us to directly compare the predictive value of self-reports with neural predictors of message effectiveness. Neural activity in a medial prefrontal region of interest, previously associated with individual behavior change, predicted the population response, whereas self-report judgments did not. This finding suggests a novel way of connecting neural signals to population responses that has not been previously demonstrated and provides information that may be difficult to obtain otherwise.