In 42 patients with untreated or treated multiple myeloma (MM) or benign monoclonal gammopathy (BMG) the lymphocytes and T lymphocyte subsets were determined by monoclonal antibodies and other surface markers. In untreated MM, the T cells (1077/microliters vs 1439/microliters, P less than 0.01) and especially the OKT4+ lymphocytes (700/microliters vs 950/microliters, P less than 0.05) were significantly reduced compared with a control group. The OKT8+ cells were slightly but not significantly decreased. In previously treated MM, the loss of T cells was more pronounced than in the untreated group and was primarily caused by a further reduction of OKT4+ cells. Patients with BMG revealed decreased OKT8+ lymphocytes (304/microliters vs 502/microliters, P less than 0.001), whereas the OKT4+ cells were within the normal range. Therefore, the OKT4/OKT8 ratio was significantly elevated compared with that in untreated MM patients and normal controls (3.31 vs 2.06 vs 2.13; P less than 0.005). To sum up, in MM the results revealed a reduction of T cells, mainly of OKT4+ cells, which is intensified by chemotherapy and persists even after a long therapy-free interval. The different findings of T cell subsets in BMG and MM may be a helpful criterion to differentiate between BMG and MM.