Rat intestinal disaccharidase activities were investigated during treatment with different doses of 2-[bis-(2-chlorethyl)-amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide (cyclophosphamide). In all experiments, disaccharidase activities decreased--although not too drastically--within 2--3 days after beginning treatment. Loss of activity was not reversed during the period of experimentation. Contrary to previous investigations, cyclophosphamide did not exert direct toxic effects on intestinal disaccharidases. Decrease of intestinal disaccharidase activities can be interpreted to be due to cyclophosphamide effects on the proliferation cycle of epithelial crypt cells resulting in a decreased number of full-function cells.