During the DNA replications involved in polyploidization or polytenization in Drosophila cells, not all DNA sequences are replicated to the same extent. Cytological studies have demonstrated that certain chromosome regions, such as the a-heterochromatin, are in some cells under-replicated and in other cells not replicated at all. Similarly, such DNA fractions as the highly repeated satellite DNAs are also under- or non-replicated in polyploid and polytene cells. The genes for rRNA in polytene cells replicate one to three rounds less than the euchromatic DNA and are capable of differential synthesis to compensate for deficiencies. The differential replication of DNA sequences indicates that there is regulation of DNA replication at a level intermediate between the replicon and the entire genome. Chromosomes of terminally differentiated polyploid or polytene cells have several domains of DNA sequences, which in replication are controlled as units. This paper, which reviews the literature on differential replication of DNA in Drosophila, discusses possible controls over this process.