The effects of chemotherapeutic agents on mouse myeloma and bone marrow precursor cells were studied using cell culture and spleen colony assay techniques, and the results were assessed for their values in predicting therapeutic effectiveness. For cyclophosphamide, nitrogen mustard, and 1,3 bis (2 chloroethyl)-1-nitrosourea (BCNU), selective toxic effects on mouse myeloma (Adj. PC-5) cells were seen while no such differential effect was observed for 5-fluorouracil. The differential effects of these agents could not be explained by the cell cycle effects but appeared to be dependent on the intrinsic properties of the two cell classes. Marked differences were noted in the sensitivity of three mouse myelomas to melphalan. The ratio of the melphalan dose required to reduce marrow CFU to 37% (D37) to the dose required to reduce myeloma CFU equally was 75 for Adj. PC-5, 18 for MOPC 46B, and 7 for MOPC 460D. These results predict that melphalan would be more effective than 5-fluorouracil for Adj. PC-5 and that melphalan would be relatively ineffective for MOPC 460D. These predictions were confirmed by survival tests.