A timed sequential chemotherapeutic regimen for multiple myeloma was designed, based on plasma cell kinetics. A randomized study comparing this regimen with the combination of intermittent melphalan and prednisone was started after an adequate pilot study. Studies with tritiated thymidine labeling and mitotic indexes were performed on patients treated with sequential therapy. Of 13 patients treated with the combination therapy, the responses were as follows: two, objective improvement; nine, subjective improvement; and two, no responses. Of nine patients treated with sequential therapy, the responses in six patients who could have evaluations were as follows: one, objective improvement; two, subjective improvement; one, no response; one, with progressive disease; and one, cardiac death. The two studies showed differences in pertubation of cell kinetics of myeloma that may be related to exponential growth and immunoglobulin types.