To describe pancreatic function during the first year of life in infants diagnosed with cystic fibrosis (CF) using serial fecal elastase measurements. This was a longitudinal study of 82 infants diagnosed with CF through newborn screening. Monthly stool samples were sent to a central laboratory for fecal elastase measurements. A total of 61 infants had an initial stool sample obtained at age <3.5 months and a final stool sample obtained at age >9 months. Twenty-six of 29 infants with a fecal elastase value <50 μg/g at study entry had a fecal elastase value <200 μg/g (the accepted cutoff value for pancreatic insufficiency) on all measurements during the year; all 29 had a value <200 μg/g at the end of the study. Of the 48 infants with initial fecal elastase value <200 μg/g, 13 had at least 1 fecal elastase value >200 μg/g but had a final stool fecal elastase value <200 μg/g; however, 4 infants with an initial fecal elastase value <200 μg/g ended the year with a value >200 μg/g. Eleven of 13 infants with an initial fecal elastase value of >200 μg/g still had a value >200 μg/g at the end of the first year. Infants with CF exhibit variability in fecal elastase values during the first year. Infants with a fecal elastase level of 50-200 μg/g at diagnosis should be treated with pancreatic enzyme replacement therapy, but fecal elastase should be remeasured at age 1 year to ensure that those with a falsely low value do not continue to receive pancreatic enzyme replacement therapy unnecessarily. Those with a fecal elastase value >200 μg/g initially can become pancreatic insufficient with time.