To initiate the experimental exploration of the role of extracellular macromolecules in influencing developmental events in the heart, a 3-dimensional substrate culture model of the developing cardiac cushion was devised. One cardiac jelly component, hyaluronic acid, was tested for its effects on morphology and migratory capacity of cushion tissue cells within the collagen matrix substrate. Hyaluronate treatment resulted in: (1) an increase in the number and extent of filopodia, reflected as an increase in cell surface area, and (2) an increase in migratory capacity, reflected as an increase in maximum depth to which cells migrate through the collagen lattice. These results suggest one major role for hyaluronate in the early cardiac cushion is the promotion of a high level of motility capability in the newly seeded cushion tissue cells, required for the key event of cell migration across the developing cushion.