Acute myelogenous leukemia (AML) of the inbred Wistar/Furth (W/Fu) rat is pathophysiologically similar to human AML. Subcutaneous transplantation of 1.0 ×106 cells of a clonal tissue culture line of W/Fu AML into 6- to 8-week-old rats produced local myeloblastomas in 8–10 days which progressed to infiltration of regional nodes, replacement of > 90% of the bone marrow, ascites, and fatal peripheral blood leukemia with concomitant hyperlysozymemia. Single doses of adriamycin, daunomycin, actinomycin, cytosine arabinoside, or Cytoxan® in rats with 1.0 cm myeloblastomas produced complete tumor regression while busulfan, vinblastine, vincristine, dexamethasone, and Methotrexate® were relatively ineffective. Responses were associated with delay in progression to peripheral blood leukemia and prolonged survival. Similar results were obtained following treatment of rats with already disseminated leukemia. The demonstration of response to drugs known active against human AML indicates that the W/Fu AML should be a valuable model for rapid evaluation of new chemotherapeutic agents for clinical use.