A glyceride derivative of chlorambucil (2), 1,3-dipalmitoyl-2-[4-[bis (2-chloroethyl)amino]benzenebutanoyl]glycerol (1), was synthesized and tested as an orally administrable antineoplastic drug endowed with lymphotropic properties. A significantly higher efficacy (increased life span) and a reduced toxicity of 1, relative to 2, were apparent when both compounds given per os were evaluated against P388 leukemia subcutaneously implanted in mice, a situation where the tumor cells disseminate along the lymphatic route. In order to assess the selective absorption of 1 by the intestinal lymphatic system after oral administration, we determined plasma and intestinal lymphatic concentrations and compared them with that obtained with 2. The results clearly demonstrate that the esterification of 2 to a diacylglycerol moiety brings about considerably higher levels in the lymph and reduces plasma levels. Moreover, pharmacokinetic and biological data suggest that 1 is most probably acting by itself rather than as a prodrug of chlorambucil.