Laminin, an extracellular matrix glycoprotein, has been implicated in a wide array of biological activities. Its specific roles during development, however, remain to be elucidated. In this report we describe the specific contribution of laminin to histogenesis and organogenesis during Drosophila embryogenesis. In particular, the function of laminin during mesoderm development and morphogenesis was dissected by analyzing embryos deficient in laminin A chain alone or in both laminin A and B2 chains. We show that laminin function is not required for the early phases of mesoderm patterning and morphogenesis in embryos at the extended germ band phase (stage 11). However, laminin function is required for the proper morphogenesis of the heart, somatic mesoderm, and the gut during later stages of embryonic development. In laminin A-deficient embryos, the heart is "broken" as a result of dissociation of the pericardial cells. The somatic myotubes are defective and do not extend properly, and the ventral oblique muscles never reach their proper attachment sites. Finally, during midgut formation, the endoderm fails to undergo the initial columnar polarization in the absence of functional laminin. These studies indicate that the primary function of laminin is to provide structural support for the various cell types, thereby enabling their proper organization into the various organs.