Age-related changes in the activities of fatty acid synthetase and palmitoyl-CoA synthetase (EC 6.2.1.3) have been determined in rabbit brain from the foetal stage through to maturity. 2. Fatty acid synthetase was most active in the soluble fraction of brain homogenates at 5 days of age, prior to the active phase of myelination. Palmitic acid was the major fatty acid synthesised throughout development. 3. Palmitoyl-CoA synthetase had a constant specific activity in the full homogenate, but in the microsomal fraction reached a maximum specific activity at 15-20 days of age. The specific activity was higher than in the mitochondrial fraction which declined from birth. Most of the palmitoyl-CoA synthetase activity was present in the fraction containing cell membranes plus nuclei. 4. From a comparison of the total activities of the enzymes involved in the metabolism of fatty acids in the brain, de novo fatty acid synthesis may be rate limiting compared with esterification of synthesised fatty acids, but not in the further transformations of the synthesised fatty acids.