Many holometabolous insects require a period of maturation following eclosion, during which they acquire full adult function. In adult flies, the events of maturation include elimination of specialized structures required for eclosion and stereotyped behaviors that lead to wing expansion and cuticle tanning. These events are regulated by a complex neuroendocrine network, which is known to involve bursicon and eclosion hormone and which can be inhibited by restraint of an adult fly immediately after eclosion. In the fruit fly, Drosophila melanogaster, maturation also includes events within the midgut, specifically, peritrophic matrix formation and morphological changes at the cardia-midgut junction. To determine how maturation in the midgut is regulated, the events of midgut maturation were examined in restrained adults and in various hormone defective mutants (rickets, baetone, and apterous) at different times after eclosion. The results were then compared to those events in unrestrained wild-type adults at the same time points. Midgut morphology and peritrophic matrix formation were examined in Periodic Acid-Schiff stained sections of whole adult flies. The relative expression of the Antigen 5-related (Agr) gene, which produces a component of the peritrophic matrix, was also determined at various times after eclosion by semiquantitative PCR. The results suggest that midgut maturation is hormonally regulated and is controlled by mechanisms similar to those that regulate maturation events outside the midgut. Maturation may be a general phenomenon that occurs in most organ systems, and which is coordinated by a common neuroendocrine mechanism.