The Drosophila gap gene Krüppel (Kr) displays a complex spatiotemporal pattern of expression during embryogenesis. Using P-element transformation experiments, we demonstrate that control elements guiding Kr expression in the central or in the anterior domain at the blastoderm stage are each composed of multiple subelements that interact synergistically. We provide evidence that bicoid (bcd) and hunch-back (hb) gene products, as well as at least one other activator, are needed to activate Kr expression in the central domain. We localize and describe regulatory elements within the 4.1-kilobase region proximal to the Kr promoter that are responsible for expression in the ectoderm, mesoderm, amnioserosa, and nervous system. Finally, a protein instability motif encoded in the second exon appears to be important for resetting the dynamic Kr pattern.