The generation of the anterior-posterior segment pattern in the Drosophila embryo requires two closely linked processes. First, the correct number of segments must be established. This is achieved by the concerted action of maternal coordinate genes and zygotic segmentation genes of the gap, pair-rule, and segment polarity classes. Second, each segment must acquire a unique identity depending on its position along the anterior-posterior axis. The latter process is controlled by the homeotic selector genes of the Antennapedia (ANT-C) and bithorax complexes (BX-C) (Akam, Development, 101, 1-22, 1987; Ingham, Nature, 335, 25-34, 1988). The members of the ANT-C and BX-C are among the best-characterized genes active in the Drosophila embryo. The basal units of their action are parasegments (PS) whose borders are out of phase with the borders of the segments which are seen in the mature embryo (see Fig. 1). The correct spatial expression of the homeotic selector genes of the ANT-C and BX-C is controlled at three different levels. Early in development, the maternal coordinate and the zygotic segmentation genes activate transcription of homeotic selector genes in a parasegmental frame. Later in development, the trans-regulatory Polycomb (PC) group genes repress the homeotic selector genes outside their domains. In addition, the homeotic selector genes repress each other, thereby maintaining the borders between their expression domains. Two observations suggested the existence of other homeotic genes active in the head and tail. First, loss-offunction mutations in the homeotic selector genes cause transformations only in the overtly segmented body region of the Drosophila embryo from PS 0 to 15, which correspond to posterior head, thorax, abdomen, and anterior tail. The extreme ends of the embryo, the anterior head and the posterior tail, are not affected in any homeotic selector gene mutation (Fig. 1). Second, the general rule that certain PS are simply transformed into anteriorly adjacent ones in selector gene mutations does not hold true for the posterior head and the anterior tail. Recently, two novel homeotic genes, spalt (sal) and fork head W h ) , have been identified for which the term regionspecific homeotic genes has been coined. In contrast to the homeotic selector genes of the ANT-C and BX-C, these genes act in two separate regions of the embryo. Both genes map outside the ANT-C and BX-C regions of the genome, and they do not share the homeodomain characteristic for the protein products of homeotic selector genes. Here, we review the genetic and molecular analysis of this class of homeotic genes. sal andflh mutations cause transformations in the head and tail of the Drosophila embryo