Natural killer (NK) activity and NK-related cell surface markers (CD16, CD56, CD57) of peripheral blood lymphocytes were studied in patients with multiple myeloma and MGUS (monoclonal gammopathy of undetermined significance). A strong correlation (p < 0.0001) was found between the numbers of cells positive for the different NK cell surface markers. The proportion of CD16+cells correlated highly to the lytic capability (lytic units/106cells) of K562 cells (p < 0.0001). High NK activity and high numbers of cells with NK-related cell surface markers were found in patients with a low tumor burden compared to controls, whereas low values were seen in patients with an advanced disease. The results indicate that NK cells might be involved in the disease process in monoclonal gammopathies, perhaps by exerting a regulatory function on the proliferating B-cell clone.