Reference equations for ventilatory function that use different statistical models may introduce artifacts that affect the estimated change of lung function during growth in young subjects. The effect of differently modelled reference equations on the estimated annual change of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in young patients with chronic lung disease was assessed. Four frequently used reference equations were used to describe the longitudinal changes of FEV1 and FVC in 52 patients (23 females) with cystic fibrosis (CF) during a mean follow-up of 3.9 yrs. Choice of reference equations directly affected value and, most importantly, estimated annual change of FVC and FEV1. Mean+/-SD annual change of FEV1 varied from 2.2+/-6.2 to -2.2+/-3.6% of predicted. For two reference equations the estimated individual changes of FEV1 and FVC in CF were positively correlated with mean individual age. This probably reflects underestimation of deteriorating lung function. Variability of annual change was independent of age only when reference equations that were designed to accurately predict lung function during the pubertal growth spurt were used. These findings have implications for patient care and clinical research.