Nine patients with cystic fibrosis but without digital clubbing (Group A) were matched, prospectively, by sex and approximate age to 9 cystic fibrosis patients with digital clubbing (Group B) and to 9 normal persons (control subjects). Patients in Group B had significantly (P less than 0.05) lower clinical scores and forced vital capacity than did those in Group A, indicating more severe pulmonary disease in the former; however, other spirometer tests of pulmonary function revealed no differences between Groups A and B. The degree of digital clubbing had significant (P less than 0.05) linear relationships to forced vital capacity (r = -0.73) and clinical scores (r = 0.853) for Groups A and B. Plasma concentrations of prostaglandins F2alpha and E were significantly increased (P less than 0.05) in both Group A (X +/- SE, 0.48 +/- 0.03 and 0.87 +/- 0.10 ng per ml, respectively) and Group B (X +/- SE, 0.68 +/- 0.04 and 1.81 +/- 0.16 ng per ml, respectively) compared to the control group (X +/- SE, 0.14 +/- 0.01 and 0.39 +/- 0.02 ng per ml, respectively). Group B had significantly larger concentrations than did Group A; however, plasma concentrations of prostaglandin 15-keto-13, 14-dihydro metabolite were not different in Groups A and B, and were significantly smaller than in the control group. These studies suggest that the degree of digital clubbing in cystic fibrosis is related to the severity of the pulmonary involvement and that the prostaglandin system may play an important role in this disease.