Hydra’s buds develop from cellular modules in the budding region through the interaction of quanta of epithelial and interstitial cells. Symbiogeny may have played two constructive and creative roles in the evolution of Cnidaria and budding: Amoeba equipped with an extrusion apparatus may have set in motion the evolution of cnidarian interstitial cells and cnidocytes; modifying the mechanism of cellular rejection may have generated asexual reproduction via budding. These conjectures suggest that early in the Neoproterozoic Era, ancestors of cnidocyst-bearing amoebae infected cellular mats resembling the contemporary Placozoa. The primitive epithelium’s attempt to reject foreign amoebae failed but led to the formation of permanent symbiogenic relationships and contemporary hydras’ ability to reject specific quantities of excess cells in buds. Supporting these conjectures is evidence that hydras fill bud modules as a function of growth rate, while “epithelial animals”, hydras deprived of interstitial cells, fail to maintain budding despite being force-fed and growing. “Epithelial animals” resume budding, however, following the reintroduction of interstitial cells suggesting that hydra’s epithelia require a quantum of interstitial cells to trigger the eruption of buds from modules.