Materials and Methods

Drugs Pure crystalline rapamycin and 29-demethoxyrapamycin (AY-24,668) were prepared as described previously2, 9). 5-Fluorouracil (5-FU, 99% pure) was obtained from Aldrich Chemical Co., Milwaukee, WI, and cyclophosphamide (CYP, 99% pure) from Polyscience Inc., Warrington, PA. Adriamycin (ADR) was purchased from a local drug store; each vial contained 10 mg doxorubicin• HCl and 50 mg lactose. For injection, rapamycin was dissolved in absolute ethanol containing 1.0 mg butylated hydroxyanisole/ml, and one volume of this solution was mixed with nine volumes of 10% Cremophor EL (BASF, Aktiengesellschaft, West Germany) in water. Sterile physiological saline was used as a vehicle for the three reference drugs. All drug solutions were prepared just before use. Tumor Models and Animals

P338 lymphocytic leukemia, B16 melanocarcinoma and Colon 38 tumor lines were obtained from the Mason Institute, Worchester, MASS., a tumor bank for the NCI. The tumors were serially transplanted in appropriate strains of inbred mice: P388 in DBA/2, B16 in C57/B1 and Colon 38 in BDF, mice. Male BDF1 mice (18~ 20 g) were used in the antitumor tests. All mice were purchased from Jackson Laboratories, Bar Harbor, ME., and were of specific-pathogen-free (SPF) grade. Antitumor Tests