A systematic study of the distribution of Paneth cells in disease of the small and large intestine is described. In disease of the small intestine and appendix there is usually a fall in the number of Paneth cells normally present. Occasionally, as in Crohn's disease, there may be proliferation. In disease of the colon the number of Paneth cells is unaltered in functional and developmental disorders and increased in the inflammatory and neoplastic diseases. It is suggested that the Paneth cell proliferation originates from stem cells in the colon. The significance of an increase in Paneth cells is discussed and it is suggested that in ulcerative colitis it may produce a self-perpetuating and destructive state.