BACKGROUND The 13C-octanoic acid breath test, a noninvasive method for measuring gastric emptying, was used to compare the gastric-emptying rate of formula-fed and breast-fed infants. Octanoic acid, a medium-chain fatty acid marked with the stable isotope 13C is immediately absorbed in the duodenum. Because gastric emptying is the rate-limiting step for the absorption of medium-chain fatty acids, the fraction of 13C expired in the breath indicates the rate of gastric emptying. METHODS Twenty-nine newborn infants (16 boys, 13 girls) were investigated, with parental consent. The infants had a mean gestational age at birth of 34.5 weeks (range, 27-41 weeks) and a birth weight of 2148 g (range, 960-4100 g). Their mean weight on the day of the test was 2496 g (range, 1998-4140 g), and their mean age was 23 days (range, 7-74 days). Each infant received a test meal after a maximum fasting period of 3 hours. Fourteen infants were fed formula milk (Nutrilon Premium, NV Nutricia, Zoetermeer, The Netherlands) with 13C-octanoic acid and 15 infants received expressed mother's milk mixed with 13C-octanoic acid. After obtaining two basal breath samples and the feeding, breath samples were collected using a nasal prong, every 5 minutes during the first half hour and every 15 minutes during the next 3.5 hours. Analysis of the expired 13C fraction in the breath samples was performed using isotope-ratio mass spectrometry, and the gastric emptying curve and gastric emptying parameters were determined. RESULTS The mean half-emptying time determined by the 13C-octanoic acid breath test was 65 minutes (range, 27-98 minutes) for the formula fed infants and 47 minutes (range, 16-86 minutes) for the breast-fed infants. The difference between the half-emptying times is significant (t-test, p < 0.05). CONCLUSIONS The results of the 13C-octanoic acid breath test indicated faster gastric emptying of human milk than formula. Our findings are in accordance with those in earlier studies, using the invasive-dilution technique; noninvasive and detailed ultrasonography, which is not easily used because it is operator dependent and the observation time is short; or cineesophago-gastroscintigraphy, which is less suitable for infants (because of the radiation involved). The 13C-octanoic acid breath test is a safe and noninvasive method for measuring gastric emptying in small infants and allows comparison of various feeding methods.