We report a test of the hypothesis that the high frequency of cystic fibrosis (CF) in Caucasian populations is due to a fertility advantage in CF carriers. One hundred forty-three grandparent couples of Utah CF cases were compared with 20 replicate sets of matched control couples drawn from the Utah Genealogical Database. Ascertainment correction, which has not been applied in previous studies of CF carrier fertility, was applied to these data. Before ascertainment correction was applied, CF carriers appeared to manifest a significant fertility advantage over controls. After the correction formula was applied, this difference disappeared. Carriers and controls were also compared in terms of the length of intervals between births. Again, no significant differences were found. It was concluded that fertility differences are unlikely to account for the observed Caucasian CF gene frequency. Other mechanisms, particularly a past selective event or random genetic drift, are more likely to be responsible.