The recovery of immunoregulatory cells in the peripheral blood of patients with multiple myeloma receiving maintenance therapy with interferon alpha 2 beta (IFN-alpha 2 beta) after intensive therapy with high-dose melphalan and autologous bone marrow or peripheral blood stem cell rescue was studied. IFN-alpha 2 beta significantly inhibited the recovery of CD3+, CD4+, CD8+, CD56+/CD3- and CD16+/CD3- lymphocytes compared with numbers found in patients who had no further post-transplant treatment, but had no effect on the recovery of CD19+ cells. Among patients who did not receive IFN-alpha 2 beta, the number of CD8+, CD56+/CD3- and CD16+CD3- lymphocytes recovered to values similar to normal volunteers with increasing time after intensive therapy, however the number of CD4+ cells remained significantly below levels found in normal volunteers. Although CD16+/CD3- and CD56+/CD3- cell numbers were reduced in patients receiving IFN-alpha 2 beta, natural killer (NK) activity was not affected. The levels of soluble interleukin 2 receptor (sIL-2R) were similar in all patients and IL-2 was not detected in any patient. At the time of writing, of the total of 69 patients, seven have relapsed, of whom three were receiving IFN-alpha 2 beta, however there was no correlation between the absolute numbers of any lymphocyte subset with imminent relapse. The data suggest that the recovery of a specific lymphocyte subset(s) in peripheral blood is unlikely to be associated with the maintenance of response after intensive therapy.