Avicelase I and Avicelase II purified from the cellulolytic thermophile Clostridium stercorarium acted in synergism to hydrolyze microcrystalline cellulose. The degree of synergism proved to be dependent on the ratio of the two enzymes and on the type of the cellulosic substrate. The activity of the combined enzymes towards Avicel was about double the sum of the individual activities. No synergism was found with amorphous cellulose preparations. It is shown that the simultaneous concerted action of both Avicelases is required to observe synergism. We suggest that synergism results from an exo-exo type cooperativity and present a mechanistic model explaining the synergistic interaction between Avicelase I and Avicelase II.