The fatty acid content of liver was determined during the last trimester of infant growth and first 4 months of life in order to estimate fatty acid levels of developing liver and to assess minimal fatty acid requirements for tissue synthesis. Accretion rates were computed by regression analysis on fatty acid determinants of total liver lipid extracts from infants of varying developmental ages. During the last trimester of liver growth, accretion of most fatty acids paralleled increases in liver weight with the exception of C18:3, omega-3. This fatty acid remained at consistently low levels during the last trimester and represented less than 10% of total omega-3 fatty acids present in liver, even though significant accretion of longer chain omega-3 homologues occurred during the final trimester. For the term infants studied, significant increase in liver weight did not occur during the early weeks of life. However, liver levels of major fatty acids declined during the first five weeks of life apparently reflecting mobilization of saturated, omega-9 and omega-3 fatty acids from liver. During the first four months of life C18:2, omega-6 and total omega-6 fatty acid content of liver increased about 3.5- and 2-fold, respectively. After the initial 5 week lag net accretion of other fatty acid components also occurred in the developing liver. These developmental changes in fatty acid components of liver are quantitatively relevant to estimating the magnitude of the potential essential fatty acid reserve that may be present in liver of the developing human neonate.