The position-specific (PS) integrins of Drosophila are a family of cell surface heterodimers that function as receptors for extracellular matrix molecules. In this study we used time-lapse videomicroscopy to examine living embryos lacking both maternal and zygotic expression of the genes that encode the alpha PS1, alpha PS2, and beta PS integrin subunits. We demonstrate roles for these molecules as early as gastrulation. Abnormalities in mutant embryos include: separation and twisting of the embryonic germband, abnormal shape and migration of midgut primordia, irregular visceral mesoderm, detachment of amnioserosa cells, rupture of the cuticle along the dorsal midline, lack of midgut constriction, and detachment of somatic muscles. These observations suggest multiple roles for PS integrins in the adhesion of cells and in the formation, organization, and migration of embryonic tissues. We also show that although alpha PS1 beta PS and alpha PS2 beta PS are often expressed in adjacent embryonic tissues, this distribution does not necessarily reflect equivalent requirements. Furthermore, the complete loss of both alpha subunits does not produce all of the phenotypes observed in embryos lacking beta PS. This suggests that alpha PS1 beta PS and alpha PS2 beta PS are not required in all embryonic processes utilizing PS integrins.