We have isolated and characterized a novel gene, named 18 wheeler (18w) for its unique segmental expression pattern in Drosophila embryos and expression in cells that migrate extensively. 18 wheeler transcripts accumulate in embryos in a pattern reminiscent of segment polarity genes. Mutations in 18w cause death during larval development and early adulthood. Escaping mutant adults often display leg, antenna, and wing deformities, presumably resulting from improper eversion of imaginal discs. Sequence analysis indicates that 18w encodes a transmembrane protein with an extracellular moiety containing many leucine rich repeats and cysteine motifs, and an intracellular domain bearing homology to the cytoplasmic portion of the interleukin-1-receptor. Expression of 18W protein in non-adhesive Schneider 2 cells promotes rapid and robust aggregation of cells. Analysis of the expression of 18w in different mutant backgrounds shows that it is under control of segment polarity and homeotic genes. The data suggest that the 18W protein participates in the developmental program specified by segmentation and homeotic genes as a cell adhesion or receptor molecule that facilitates cell movements.