nautilus (nau), one member of the myogenic regulatory family of bHLH-encoding genes, is expressed in a subset of muscle precursors and differentiated fibers in the Drosophila embryo. To elucidate the role of nautilus in myogenesis, we have misexpressed it using the GAL4-targeted system. We find that ectopic expression results in lethality throughout Drosophila development. We analyzed the effects of embryonic expression in mesodermal tissues that include the cardioblasts of the dorsal vessel as well most, if not all, of the presumptive somatic muscle precursors. Immunohistochemical staining for muscle MHC revealed abnormalities that include an absence of cardial cells, coincident with the appearance of novel muscle fibers adjacent to the dorsal vessel. Moreover, many cardioblasts express increased levels of muscle-specific genes such as myosin, actin 57B, and Mlp60A, a protein that is restricted to the somatic, visceral, and pharyngeal muscles. These data suggest that the missing cardial cells have been transformed into cells with properties similar to those of the somatic muscles. In addition, ubiquitous expression of nautilus in somatic muscle cells of these embryos resulted in muscle pattern defects. Specifically, muscles that do not normally express nautilus were frequently absent, and novel fibers were observed in positions reminiscent of nau-expressing muscles. These data imply that nautilus can alter the developmental program of muscle precursors. In summary, we suggest that nautilus induces myogenic differentiation in vivo when ectopically expressed in developing cardioblasts and may affect the myogenic differentiation program of specific muscle fibers.