While anterior/posterior chest x-rays (CXR) are routinely performed to estimate lung volume (LV) and adjust ventilator settings, the precise measurement of LV requires additional sophistication. In 31 infants ventilated because of surfactant deficiency (n=23), bronchopulmonary dysplasia (n=7), or pulmonary hypoplasia (n=1) with either intermittent positive pressure (n=18) or high frequency oscillation (n=13) (gestational age 23-39 weeks (median 26 weeks); birthweight 550-2780 g (median 840 g); age at measurement 1-91 days (median 6 days); weight at study time (WST) 675-3000 g (median 938 g)), we investigated whether LV, as measured by the sulfur hexafluoride (SF6) washout technique, could by estimated from CXR by: 1) the sum (A+B) of the right (A) and left (B) lung fields areas; 2) the product (LxW) of the distances from the right apex to the right costophrenic angle (L) and between both costophrenic angles (W); 3) the diaphragm position relative to the posterior parts of the ribs (DP); and 4) the lung radiolucency (RL, grades 0-4). Correlations between A+B (r=0.44) or LxW (r=0.37) and LV were poor, but improved when A+B, LxW, and LV were normalized to WST: (A+B)/WST vs. LV/WST (r=0.74), and LxW/WST vs. LV/WST (r=0.67). DP (r=0.13) and RL (Spearman's rho=0.17) did not correlate with LV/WST. A multiple linear regression analysis led to the following best-fit equation: LV/WST=2.58 (A+B)/WST - 5.47 DP + 42.2 (r=0.83). We concluded that an estimate of LV from CXR lacked sufficient accuracy. DP and RL did not correlate with LV measured by SF6 washout.