In the course of millions of years of extraordinary evolutionary success, termites have developed a unique cellulose-digestion system which provides energy and nutrition from what are otherwise considered nutritionally poor food sources, such as wood and humic matters. Lower termites, equipped with both endogenous and symbiotic cellulases, primarily feed on wood and wood related products. Therefore, although they make up only a quarter of the known termite species, lower termites are responsible for the majority of economic damage worldwide. Here, we investigated the diversity, structure, and identity of four cellulases in a lower termite, Reticulitermes flavipes. These four genes, one endogenous (Cell-1) and three symbiotic (Cell-2, 3, and 4), encode distinct and unique cellulase proteins with significant homology to endoglucanases, exoglucanases, and xylanases of termite or symbiotic origins. It is also noteworthy that intron-1 form Cell-2 is the first intron sequence reported from a termite symbiont; and one of the first introns ever sequenced from a protozoan. By ways of quantitative PCR and enzymatic assays, we are able to correlate individual cellulase gene expression with specific cellulotic activity throughout the entire digestive tract of R. flavipes. Nakashima et al. [Nakashima, K., Watanabe, H., Saitoh, H., Tokuda, G., & Azuma, J. I. (2002) Insect Biochem. Mol. Biol. 32, 777-784] proposed that there are two separate cellulose-digesting systems working independently in the lower termite Coptotermes formosanus, whereby one endogenous cellulase system exists in the midgut, and the other symbiotic protozoan system exists in the hindgut. Our findings, alternatively, suggest a system of collaborative and sequential cellulose digestion in R. flavipes.