Chalones specifically inhibit cell rpoliferation not only in their respective normal cell system, but also in the malignant descendants of these cells. Consequently, a number of hypotheses have been put forward as to how chalones could be used in cancer treatment or related areas. As chalones are not cytotoxic themselves, but merely inhibit proliferation, the regression of tumors which have been observed in some cases must have been caused by other mechanisms, not directly related to the increased chalone level. Some of the potential advantages and drawbacks of this direct approach will be discussed. Some models in which chalones serve as adjuncts to other forms of therapy will be discussed. The experimental testing of these procedures and hypothesis is hampered severly by the unavailability of satisfactory chalone preparations. A possible approach to overcome this by using synthetic granulocytic (and possibly other) chalone(s) is discussed in detail.