A total of 96 peripheral blood stem cell harvests (PBSCH) were collected following standard chemotherapy from 27 patients with leukemia, lymphoma, and myeloma. Tumor molecular markers were analyzed in diagnostic samples by Southern blot [immunoglobulin heavy chain (IgHJ), T cell receptor (TcR) delta chain, TcR beta chain] and polymerase chain reaction (PCR) amplification [IgH, TcR delta, t(14;18) translocation] and found in 11 of 22 and 13 of 27 patients, respectively. At a sensitivity of 2 to 5%, Southern blot analysis failed to detect tumor in PBSCH. Using PCR with sensitivities of 10(-4) (IgH, TcR delta) to 10(-6) [t(14;18)] tumor was present in 34 PBSCH collected from five patients with acute lymphoblastic leukemia and two with lymphoma. In these patients, PBSCH collected after successive courses of chemotherapy remained consistently positive. However, no tumor was detected in 28 PBSCH from five patients with lymphoma and one with myeloma. Of eight patients who had bone marrow examined (six concurrently) within 3 weeks of PBSCH, one had tumor in the PBSCH but not in the bone marrow, and three had tumor in the bone marrow but not in the PBSCH, indicating a possible advantage in using PBSC for autologous transplantation in these patients. Although PBSC are an alternative source of stem cells to bone marrow and are considered to have a lower incidence of tumor contamination, the majority of PBSC in this study were positive by PCR analysis. PCR analysis was unable to determine if a positive result represents clonogenic cells capable of initiating relapse following transplant.