BACKGROUND Air-displacement plethysmography (ADP) was developed as a noninvasive tool to assess body composition, i.e., the proportion of fat mass (%FM) and lean body mass. The results of previous studies comparing ADP with labeled water dilution in infants and with chemical analysis in phantoms have validated the ADP approach indirectly. We assessed the precision and accuracy of measurements of % FM proportions in live animals, using ADP in comparison with biochemical analyses. METHODS Three groups of 12 piglets each underwent four consecutive body composition assessments at 2, 7, and 21 d and were euthanized to determine whole-body lipid content by direct chemical analysis. RESULTS The average body weights were 1,490, 2,210, and 5,610 g at d2, d7, and d21, respectively. The mean %FM values determined by biochemical analysis and ADP were 8.63 ± 4.08% and 8.01 ± 4.03%, respectively. Linear regression and Bland-Altman analyses indicated good agreement for %FM. The root mean square coefficient of variation (RMS-CV) for ADP was 17.9%, with a better precision in the higher fat mass range. CONCLUSIONS Despite its relatively poor precision in the low range of %FM, ADP measures fat mass with reasonable precision and accuracy in the range of body weight encountered in low-birth-weight infants.