Fatty acid esterification was measured in fetal jejunal and ileal isografts implanted under the kidney capsules of adult host rats and compared to the age-controlled intestine grown in situ. Studies were conducted on the 21st, 35th, 49th, and 63rd postconceptional days, corresponding to prenatal, suckling, weaning, and weaned rats. Substantial fatty acid esterification activity was found in prenatal jejunum but not in ileum. A proximal-distal gradient of fatty acid esterification was observed in all groups grown in situ, but not in isografts. The monoglyceride pathway (MG-P) accounted for about one-third of total fatty acid esterification (TFAE) in jejunum grown in situ and remained constant through the study. In the ileum, MG-P was the major esterification pathway during the first 4 postnatal weeks, but decreased progressively after weaning to become insignificant in adult rats. TFAE fell in the jejunal isografts, whereas it increased in the ileum. MG-P remained as the major pathway in the implanted jejunum and ileum. Our studies suggest that luminal contents are probably the most important modulator for the development and maintenance of intestinal fatty acid esterification, and "fetal programming" manifested by changes in fatty acid esterification mechanisms in the isografts is less important.