We have developed a new technique that allows assessment of infant lung function over an extended volume range. The lungs are rapidly inflated to a predetermined inflation pressure (PP) using a modified diaphragm pump. Forced expiratory flow-volume (FEFV) curves are then generated from raised lung volumes using an inflatable plastic jacket. We studied 26 normal infants with a median age of 14 mo (range, 3 to 23 mo). FEFV curves were obtained in each infant from end-tidal inspiration and from lung volumes set by a range of PP (15 to 20 cm H2O). Mean (SE) volume above FRC was 107 ml (9 ml), and mean forced expiratory time was 0.73 s (0.05 s) at end-tidal inspiration. Both measurements increased progressively with increases in PP to 251 ml (13 ml) and 1.04 s (0.06 s), respectively, at 20 cm H2O PP (p < 0.0001). Mean intrasubject coefficient of variation was 15.5% (95% confidence interval, 12 to 19%) for maximal flow at FRC, but it was less than 6% (95% CI, 4 to 8%) for forced expiratory volume-time (FEVt) measurements at all levels of PP. Twenty-seven recurrently wheezy infants with a median age of 13 mo (range, 6 to 18 mo) were subsequently studied using a PP of 17.5 cm H2O. Wheezy infants had a lower VmaxFRC [mean (1.39 ml/s/cm) and 95% CI (1.15 to 1.63 ml/s/cm)] than did normal infants (1.78 ml/s/cm; CI, 1.51 to 2.05) (p < 0.05). FEV1 measurements were all lower in wheezy infants than in normals infants: mean FEV0.5, 1.86 ml/cm (CI, 1.73 to 1.98) and 2.31 ml/cm (CI, 2.15 to 2.48), respectively (p < 0.0001); FEV0.75, 2.20 ml/cm (CI, 2.07 to 2.32) and 2.72 ml/cm (CI, 2.52 to 2.91), respectively (p < 0.0001); FEV1.0, 2.42 ml/cm (CI, 2.26 to 2.58) and 2.84 ml/cm (CI, 2.63 to 3.06), respectively (p < 0.005). The Ci values of each FEVt measurement did not overlap between the wheezy and normal groups; however, the CI values of VmaxFRC overlapped markedly. In addition, FEVt parameters showed greater sensitivity in detecting reduced lung function (71 to 89%) than did VmaxFRC parameters (56%). We conclude that (1) FEVt measurements derived from a lung volume set by a standardized pressure are more reproducible than flow measurements in the tidal volume range; (2) FEVt measurements are significantly lower in wheezy infants than in normal infants, show less overlap than flow measurements in the tidal volume range, and therefore are better able to separate the two populations.