It has been suggested that humans may suffer a high genomic deleterious mutation rate(1,2). Here we test this hypothesis by applying a variant of a molecular approach(3) to estimate the deleterious mutation rate in hominids from the level of selective constraint in DNA sequences. Under conservative assumptions, we estimate that an average of 4.2 amino-acid-altering mutations per diploid per generation have occurred in the human lineage since humans separated from chimpanzees. Of these mutations, we estimate that at least 38% have been eliminated by natural selection, indicating that there have been more than 1.6 new deleterious mutations per diploid genome per generation. Thus, the deleterious mutation rate specific to protein-coding sequences alone is close to the upper limit tolerable by a species such as humans that has a low reproductive rate(4), indicating that the effects of deleterious mutations may have combined synergistically, Furthermore, the level of selective constraint in hominid protein-coding sequences is atypically low, A large number of slightly deleterious mutations may therefore have become fixed in hominid lineages.