A variety of mutations, including those affecting laminin expression and basement mem-brane, cause early embryonic lethality in the peri-implantation period. However, low cell numbers and inaccessibility of these small embryos make it difficult to study the molecular mechanisms that underlie these defects. Embryoid bodies cultured as suspended spherical cell aggregates derived from normal and defective embryonic stem cells provide a tractable experimental system with which the early developmental processes can be recapitulated under defined conditions. Thus, endoderm formation and maturation, basement membrane assembly and its signaling consequences, epiblast polarization, apoptosis, and cavitation can be studied using a combination of genetic, biochemical, cell, and molecular biology approaches.