It has been known for many decades that certain murine and human cancers can spontaneously mature to benign tissue. These observations have stimulated investigators to attempt to induce a state of more normal or benign differentiation in cancer cells using biologic substances or chemicals. Polar solvents including dimethylsulfoxide, dimethylformamide, and monomethylformamide have proven to be good inducers of maturational events in murine and human cancer cells. Moreover, several laboratories have demonstrated that polar solvents inhibit the growth of human tumor xenografts in nude mice. These findings have resulted in the entry of monomethylformamide into phase I clinical trials in America and Europe. Preclinical work further suggests that polar solvents may be useful agents in combination with conventional treatment modalities. The use of drugs such as monomethylformamide that can convert neoplastic cells to benign cells rather than kill the tumor cells represents an important conceptual departure from standard cytotoxic chemotherapy. The use of maturational-agent therapy should be considered as an important new development in the design of cancer treatment protocols.