This chapter deals with advantages as well as limitations of the nude mouse model with respect to maturating agents and describes methods for monitoring differentiation and proliferation in vivo. Tumor cells cultured in vitro as a monolayer seem to be an unfavorable model since culturing conditions are far from physiological and not permissive for major modulation of differentiation. A fundamental problem when studying differentiation inducers in vivo is the linkage between reduced proliferation and induced cellular differentiation, and the distinction of this latter process from the cytotoxic action of the agent. Quantification of differentiation markers can be facilitated by performing immunohisto-chemical techniques. In most studies on differentiation inducers tested in tumor-bearing nude mice, growth delay has been used as a parameter to express antitumor effects. Techniques for simultaneous monitoring of the processes of differentiation and proliferation in xenografts grown in nude mice are available.