The paired gene is one of approximately 30 zygotic segmentation genes responsible for establishing the segmented body plan of Drosophila melanogaster. To gain insight into the mechanism by which the paired gene is expressed in a complex temporal and spatial pattern, we have examined paired protein expression in wild-type and mutant embryos. In wild-type embryos, paired protein is expressed in several phases. Initial expression in broad domains evolves into a pair-rule pattern of eight stripes during cellularization. Subsequently, a segment-polarity-like pattern of fourteen stripes emerges. Later, at mid-embryogenesis, paired is expressed in specific regions of the head and in specific cells of the central nervous system. Analysis of the initial paired expression in the primary pair-rule mutants even-skipped, runt and hairy, and in all gap mutants suggests that the products of the gap genes hunchback, Krüppel, knirps and giant activate paired expression in stripes. With the exception of stripe 1, which is activated by even-skipped, and stripe 8, which depends upon runt, the primary pair-rule proteins are required for subsequent modulation rather than activation of the paired stripes. The factors activating paired expression in the pair-rule mode appear to interact with those activating it along the dorsoventral axis.