Despite the fact that the recently evolved Microcephalin and the related Abnormal Spindle-like Microcaphaly Associated (ASPM) alleles do not appear to be associated with IQ at the individual differences level, the frequencies of Microcephalin have been found to correlate strongly with IQ at the cross-country level. In this study, the association between these two alleles and intelligence is examined using a sample of 59 populations. A bivariate correlation between Microcephalin and population average IQ of r = .790 (p ≤ .01) was found, and a multiple regression analysis in which the Human Development Index, Disability Adjusted Life Years (DALY) lost due to Infectious diseases, DALY Nutritional deficiencies, and Würm glaciation temperature means were included revealed that Microcephalin remained a good predictor of IQ. Path analysis, with both direct and indirect paths from Microcephalin to intelligence, showed good model fit. These multivariate analyses revealed strong and robust associations between DALYs and Microcephalin, indicating that the former partially mediates the association between the latter and IQ. A second smaller correlational analysis involving ten country-level estimates of the frequencies of these two alleles collected from the 1000 genomes database replicated this pattern of results. To account for the findings of this study, we review evidence that these alleles are expressed in the immune system. Microcephalin is strongly associated with DNA repair, which indicates a special role for this allele in the intrinsic anti-viral immune response. Enhanced immune functioning may have advantaged both hunter–gatherer and agrarian societies coping with the heightened disease burden that resulted from population growth and exposure to zoonotic diseases, making it more likely that such growth and concomitant increases in intelligence could occur.