The effect of ricin and abrin on the survival of mice treated with L1210 leukemic cells intraperitoneally or intravenously was studied. In mice given 1 X 10(5) L1210 leukemia cells intraperitoneally a single dose of ricin (2.1 microgram/kg) intraperitoneally gave the best results, an increased life span (ILS) of 59%. Abrin also increased the life span of such animals although to a lesser extent. The effect of ricin was superior to that of 5-fluorouracil, but inferior to that of adriamycin, which gave a maximum ILS of 280%. In mice given L1210 cells intravenously no increase in life span was obtained with ricin, abrin or adiramycin, whereas 5-fluorouracil gave an ILS of 40-50%. In spleen colony assays the differential effect of ricin and abrin on the proliferative capacity of normal hematopoietic and leukemic colony-forming cells in bone marrow was studied. The differential effect of ricin was as good as that of adriamycin and considerably better than that of 5-fluorouracil. Abrin had a much smaller effect than ricin on both normal and leukemic cells. The effect of abrin on the leukemic cells was too small to be of therapeutic value. The results warrant exploration of the use of ricin in the treatment of human leukemia.