The discovery of DNA sequence amplification in sciarid flies and investigations into its control and biological significance are reviewed. Results thus far show that amplification of specific salivary gland polytene chromosome bands is a general phenomenon in sciarids. It is brought about as part of a final endoreplication cycle by the rising titer of ecdysterone that occurs as the larvae approach the prepupal period. Amplification and transcription of these bands is a late, multistep effect of this hormone. The DNA puffs which form in amplified regions produce mRNAs which are translated into polypeptides that appear to be involved in cocoon formation. Application of molecular cloning techniques to the study of DNA amplification has allowed precise quantitation of amplification for several DNA puffs and is yielding maps of their transcription units. These techniques will ultimately help to define the origins of DNA puff replication and contribute to an understanding of the mechanism and control of the amplification phenomenon in Sciaridae. Projections for future experimental approaches are presented.