The observation that mothers of cystic fibrosis patients come from sibships that are larger than those of the fathers is explained by a decrease in sex ratio with increasing size of parental sibships. This feature also provides the basis for a new theory for the dissemination of the major mutant allele, deduced to have arisen 2,700-5,000 years ago, in accordance with an overall heterozygote advantage of around 3%. In heterozygous women with heterozygous partners, sex-related selection probably occurs after fertilization.