The CF diagnosis can be difficult in subjects with disease consistent symptoms and borderline values of the sweat test. This study aimed to evaluate possibly resolutory criteria. Seventy-one ill subjects with borderline sweat test values (40-70 mEq/l Cl-) aged 0.1-37.7 years (mean, 8.7; SD, 7.3) were studied and compared with 33 age-matched CF patients (Cl- over 75 mEq/l) and 25 healthy subjects. A complex CF score based on 25 variables was set: CF-specific clinical conditions, detailed analysis of sweat test (salt-free diet test included), pancreatic function, Pseudomonas infection, and others. The score ranged from 0 to a maximum of 65 and clearly distinguished the CF patients from the healthy subjects. Therefore the CF score was assumed as the best reference criterion to define the diagnosis in the borderline group: 27 of them (38%) were assigned to the CF condition and 44 (62%) to the healthy one, with a quite clear separation between the 2 subgroups. With respect to these assignments, the most discriminant variable turned out to be the sweat Cl- persisting above 40 mEq/l after 5 days of salt-free diet (mean error, 18.4%). Neither sweat Cl-/Na+ ratio nor bicarbonate duodenal output showed better discriminant power (mean error, 29% and 25%, respectively). It is concluded that in borderline situations of sweat test results a definite CF diagnosis can be achieved only by compounding many clinical and laboratory data with a preference for the sweat test after a salt-free diet period. The CF score proposal can be an effective help.