Patients with monoclonal gammopathy secrete monoclonal antibodies (M-component), that in some patients are associated with polyneuropathy. The M-component has been shown to react with peripheral nerve myelin in some of these patients. However, it is not known whether the M-component secreting B-cells are autonomous or subject to regulation by T-cells or if other cellular abnormalities may occur. In order to define circulating lymphocyte subpopulations, flow cytometry was done on blood samples from patients with monoclonal gammopathy and demyelinating polyneuropathy (n = 13) and patients with monoclonal gammopathy without polyneuropathy (n = 11), and were compared to healthy controls. Significantly increased proportions of primed T-helper (CD4+) cells, i.e. those expressing helper/inducer function (CD29+ CD4+), providing help for antibody secretion, as well as decreased proportions of naive, unprimed suppressor/inducer (CD45RA+ CD4+) T-helper cells were found in patients with M-component associated polyneuropathy. Within the T-cytotoxic/suppressor population (CD8+) we found an increased proportion of killer/effector (S6F1+ CD8+) cells and a decreased proportion of suppressor/effector (S6F1- CD8+) cells in patients with monoclonal gammopathy and polyneuropathy. Similar findings were found in monoclonal gammopathy patients without polyneuropathy, although the deviations in general were less pronounced and did not reach statistical significance compared to the controls. The proportion of natural killer (NK) cells (CD56+) was markedly decreased in all patients with monoclonal gammopathy. In the whole group of patients with monoclonal gammopathy, we found clear proportions of interleukin-2 receptor (CD25+) expressing lymphocytes, indicating the presence of activated T-cells. No clear correlation between abberations in T-cell subtypes and clinical severity of the demyelinating polyneuropathy or titres of anti-PNM antibodies was found.(ABSTRACT TRUNCATED AT 250 WORDS)