Reported values of lung resistance (RL) and elastance (EL) in spontaneously breathing preterm neonates vary widely. We hypothesized that this variability in lung properties can be largely explained by both inter- and intrasubject variability in breathing pattern and demographics. Thirty-three neonates receiving nasal continuous positive airway pressure [weight 606-1,792 g, gestational age (GA) of 25-33 wk, 2-49 days old] were studied. Transpulmonary pressure was measured by esophageal manometry and airway flow by face mask pneumotachography. Breath-to-breath changes in RL and EL in each infant were estimated by Fourier analysis of impedance (Z) and by multiple linear regression (MLR). RL(MLR) (RL(MLR) = 0.85 x RL(Z) -0.43; r(2) = 0.95) and EL(MLR) (EL(MLR) = 0.97 x EL(Z) + 8.4; r(2) = 0.98) were highly correlated to RL(Z) and EL(Z), respectively. Both RL (mean +/- SD; RL(Z) = 70 +/- 38, RL(MLR) = 59 +/- 36 cm H(2)O x s x l(-1)) and EL (EL(Z) = 434 +/- 212, EL(MLR) = 436 +/- 210 cm H(2)O/l) exhibited wide intra- and intersubject variability. Regardless of computation method, RL was found to decrease as a function of weight, age, respiratory rate (RR), and tidal volume (VT) whereas it increased as a function of RR. VT and inspiratory-to-expiratory time ratio (TI/TE). EL decreased with increasing weight, age, VT and female gender and increased as RR and TI/TE increased. We conclude that accounting for the effects of breathing pattern variability and demographic parameters on estimates of RL and EL is essential if they are to be of clinical value. Multivariate statistical models of RL and EL may facilitate the interpretation of lung mechanics measurements in spontaneously breathing infants.