Neonatal cystic fibrosis (CF) screening has been performed in New Zealand for a total of 7 years. This study reports the experience with this procedure in New Zealand over a 4 year period and compares it with 2 years when diagnoses of CF were suggested by clinical features only. A total of 72 infants were confirmed as having CF during 4 years of screening. Twenty-eight infants were found to have CF during 2 years in which screening was not performed. There were 29 false positive diagnoses during the screening years and six false negative diagnoses. Three of the false negative diagnoses occurred because of laboratory error, but three occurred because either the first or second measurement of immunoreactive trypsinogen (IRT) was normal. Faecal chymotrypsin was measured in samples from 434 infants at the time of the second IRT and assisted with the diagnosis for one infant which might otherwise have been missed. Only 42.5% of infants were asymptomatic at the time of the confirmatory sweat test. Significant morbidity and mortality was associated with meconium ileus which occurred in 24% of infants with CF. Improved ascertainment of cases of CF has occurred since screening began. Further follow-up is required to determine other benefits of newborn screening.