Synergism is usually only seen in the digestion of substrates that contain crystalline cellulose, probably because there are only a few regions in this substrate that are accessible to each cellulase. It seems likely that synergism occurs only when two cellulases attack different regions of the cellulose molecule and each one creates new sites of attack for the other enzymes in the mixture. There is no evidence that synergism requires interactions between the synergizing cellulases, as cellulases from unrelated organisms show similar synergism to those from the same organism. All good endocellulases are able to show synergism with any exocellulase, but most endocellulases do not show synergism with each other. Exocellulases show synergism with other exocellulases, but only if they attack different ends of the cellulose chains. Processive endocellulases can give synergy with all other types of cellulase (Wilson, D. B., unpublished). It is interesting that cellulose pretreated with an endocellulase is a better substrate for exocellulases than is untreated cellulose, but the reverse is not true (55). This is true, even though it has been shown in synergistic mixtures of an exocellulase and an endocellulase that endocellulase activity is increased as much in the mixture as is exocellulase activity (28). It seems likely that when an exocellulase degrades a cellulose chain, it disrupts some regions in adjacent cellulose molecules, making them more available to an endocellulase. However, over time the molecules in the disrupted regions may reform their interactions with adjacent chains, so that when an endocellulase is added, after exocellulase treatment, it is not able to utilize the transiently disrupted chains.