• The recent identification of the cystic fibrosis (CF) gene confirms that genetic heterogeneity occurs in CF. A three—basepair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product, termed the CF conductance regulator protein, accounts for 70% of cases of CF in white subjects. However, this gene defect occurs in only 37% of affected blacks. Analysis of CF genes from American blacks has revealed a number of mutations, most of which are unique to that population. We therefore searched for potential differences in expression of CF between 24 black and 48 white patients with CF matched for birth date and gender. Black patients more frequently presented with only respiratory symptoms (38% vs 10%). Black patients had fewer hospitalizations for pulmonary exacerbations (2 vs 6.9), a better mean forced vital capacity (77% vs 62% of predicted), and higher chest roentgenogram scores (18.2 vs 14.4) than white patients. Complication rates were similar except for a higher incidence of hyponatremic dehydration (21% vs 2%) and peptic ulcer disease (13% vs 0%) in blacks. Survival time appeared to be longer in blacks, but the difference was not statistically significant. We conclude that phenotypic differences exist between black and white patients with CF, which may be due to the genetic heterogeneity between these two populations.