The fushi tarazu gene is essential for the establishment of the Drosophila embryonic body plan. When first expressed, in early embryogenesis, fushi tarazu mRNA is uniformly distributed over most of the embryo. Subsequently, fushi tarazu mRNA expression rapidly evolves into a pattern of seven stripes that encircle the embryo. The instability of fushi tarazu mRNA is probably crucial for attaining this localized pattern of expression. mRNA stability in transgenic embryos was measured by a new method that does not use drugs or external interference. Experiments using hybrid genes that fuse fushi tarazu sequences to those of the stable ribosomal protein A1 mRNA provide evidence for at least two destabilizing elements in the fushi tarazu mRNA, one located within the 5 one-third of the mRNA and the other near the 3 end (termed FIE3 for ftz instability element 3). The FIE3 lies within a 201-nucleotide sequence just upstream of the polyadenylation signal and can act autonomously to destabilize a heterologous mRNA. Further deletion constructs identified an essential 68-nucleotide element within the FIE3. Lack of homology between this element and other previously identified destabilization sequences suggests that FIE3 contains a novel RNA destabilization element.mRNA stability plays a key role in regulating the expression of many transiently expressed genes, such as cytokines, oncogenes, and developmentally important genes (36). While much has been learned about the regulation of mRNA stability in cultured cells (4), few studies have been conducted with whole organisms or in a developmental context (36). This is due in part to the lack of a convenient method to assay mRNA stability in whole organisms. In this paper, we present a new method to measure mRNA stability in Drosophila embryos.We have directed our attention to genes which establish the Drosophila embryonic body plan. Early zygotic mRNAs belonging to the gap, pair-rule, and segment polarity group of genes are expressed only transiently in the developing Drosophila embryo. As such, these mRNAs are likely to be unstable, and as indicated below, instability is probably crucial for achieving correct spatial and temporal pattern of expression. Here we focus on fushi tarazu (ftz), one of the best-characterized Drosophila pair-rule genes. The ftz mRNA is among the shortest-lived mRNAs (6-to 14-min half-life) among higher eukaryotes (4, 9) and shares the cytoplasm with a majority of mostly stable mRNAs.ftz transcripts are first expressed at low levels at embryonic nuclear cycle 11 (about 1 h 40 min after egg laying at 25ЊC) in a broad band between 15 and 65% egg length (measured from the posterior pole) (5, 11, 13). During cellularization of the blastoderm (2 h 10 min to 2 h 50 min), ftz mRNA becomes transiently restricted to four broad bands and finally to seven narrow stripes that encircle the embryo (5, 13, 38, 45). Thus, it is during this very short time that the spatial pattern of ftz mRNA expression is established. Formation of stripes probably occurs by the cessati...