The major histocompatibility complex (MHC) of immunity genes has been reported to influence mate choice in vertebrates, and a recent study presented genetic evidence for this effect in humans. Specifically, greater dissimilarity at the MHC locus was reported for European-American mates (parents in HapMap Phase 2 trios) than for non-mates. Here we show that the results depend on a few extreme data points, are not robust to conservative changes in the analysis procedure, and cannot be reproduced in an equivalent but independent set of European-American mates. Although some evidence suggests an avoidance of extreme MHC similarity between mates, rather than a preference for dissimilarity, limited sample sizes preclude a rigorous investigation. In summary, fine-scale molecular-genetic data do not conclusively support the hypothesis that mate selection in humans is influenced by the MHC locus.