Fatty acyl CoA synthetase (FACS) activities were investigated in fetal, neonatal and adult liver and lung. Lung microsomal FACS activity increased near term, declined after birth and reached adult values in 30-day-old rats. Liver microsomal FACS did not show these changes near term. The post-weaning shift from a high fat diet to regular chow diet resulted in decreased liver FACS activity. Lung FACS did not respond to this change in diet. These data demonstrate that long chain FACS is present in the last 4 days of fetal life and probably contributes to the activation of fatty acids utilized as energy substrate or for the synthesis of phospholipids.