The roles of positive directional selection (selective sweeps) and negative selection (background selection) in shaping the genome-wide distribution of genetic variation in humans remain largely unknown. Here, we optimize the parameter values of a model of the removal of deleterious mutations (background selection) to observed levels of human polymorphism, controlling for mutation rate heterogeneity by using interspecific divergence. A point of “best fit” was found between background-selection predictions and estimates of human effective population sizes, with reasonable parameter estimates whose uncertainty was assessed by bootstrapping. The results suggest that the purging of deleterious alleles has had some influence on shaping levels of human variation, although the effects may be subtle over the majority of the human genome. A significant relationship was found between background-selection predictions and measures of skew in the allele frequency distribution. The genome-wide action of selection (positive and/or negative) is required to explain this observation.