Forced expiratory volume in one second (FEV(1)) is widely used to guide referral of patients with cystic fibrosis (CF) for lung transplantation. We reasoned that the best FEV(1) in a 6-month period (bFEV(1)) would be a useful marker of the need for transplant referral. We examined both the rate of decline and different threshold values of bFEV(1) as prognostic indicators in young CF patients. In a case-control analysis, rates of decline in and threshold values of bFEV(1) of 28 patients dying between ages 7-18 years from 1980-1997 were compared to those of 28 age- and gender-matched controls. The threshold analysis of bFEV(1) values was then applied to all patients under age 19 years followed in our clinic from 1993-1997. The rate of decline in bFEV(1) differed for cases and controls over the 4-year period prior to death, but not from years 2-4 prior to death, the time at which transplant referral decisions should be made. A bFEV(1) value of 50% predicted at 2 years prior to the death of the case selected 14 of 28 cases and one control. When applied to all pediatric patients followed from 1993-1997, a bFEV1 threshold of 50% predicted selected 2 of the 3 patients who died and 3 of the 140 patients who survived. Consideration of lung transplantation referral should begin when young CF patients have a best FEV(1) <50% predicted despite aggressive conventional treatment. Copyright 2000 Wiley-Liss, Inc.