Single sperm typing provides an accurate method to order tightly linked loci by single cell DNA high resolution segregation analysis. We have used similar methods to type individual sperm from a known delta F508 cystic fibrosis heterozygote to determine the frequency of the mutation within his germ cell population, and to test possible explanations for the reported sex ratio distortion of the cystic fibrosis (CF) mutation to male offspring. Using a nested polymerase chain reaction we have been able to amplify a single locus sequence, cystic fibrosis transmembrane conductance regulator (CFTR), from a single target sperm haploid genome to detectable amounts without the use of radioactivity. The same sperm from a single male delta F508 carrier were simultaneously typed for the presence of the sex chromosomes to verify the ratio of X- to Y-bearing sperm and to determine the association, if any, between sex and delta F508 in male gametes. We have demonstrated that there is a significant difference in the proportions of 'normal' and 'delta F508' sperm (X2 = 7.36, p < 0.01), although when the same sperm are sexed the difference between delta F508/X and delta F508/Y sperm is not significant (X2 = 1.71, p = 0.192). Single sperm typing can address questions about segregation distortion in man, and it is unlikely that sex ratio distortion for CF carriers is due to events which occur pre-fertilisation. As these data are from one individual only, they should be confirmed for other male carriers, including those with different CF mutations.