Many homeobox-containing genes of Drosophila regulate pathways of differentiation. These proteins probably function as promoter- or enhancer-selective transcription factors. We have isolated a new homeobox-containing gene, msh-2, by means of the polymerase chain reactions (PCR) using redundant primers. msh-2 is specifically expressed in mesodermal primordia during a short time period early in development. It first appears at blastoderm stage just before the ventral invagination of the mesoderm and shortly after twist, a gene required for mesoderm formation, is expressed. During germband elongation all the mesodermal cells in the segmented part of the embryo express msh-2, but soon afterwards msh-2 becomes restricted to the dorsal mesoderm, which includes the primordia for the visceral musculature and the heart. Prior to muscle differentiation, msh-2 expression ceases, except for two rows of cells that will be included in the dorsal vessel. Embryos that are deficient for the chromosomal region, 93C-F, which includes the msh-2 gene, show normal mesoderm invagination and dorsal spreading. However, later in development no visceral muscle and dorsal vessel differentiation can be detected, but some skeletal muscles do form, albeit abnormally. msh-2 expression, except for a patch in the head, is dependent on twist function. On the other hand, snail, another mesoderm determinant, does not appear to be required for msh-2 initiation, but is necessary for the maintenance of msh-2 expression after germband elongation. H2.0, a homeo-box-containing gene specifically expressed in visceral mesoderm, is not transcribed in the mesoderm in 93C-F deficiency embryos.(ABSTRACT TRUNCATED AT 250 WORDS)