To investigate whether there is a correlation between subtypes of plasma cells in the bone marrow and the production of M-protein, flow cytometry and serum free light chain (FLC) analyses were carried out in 17 patients with primary systemic AL amyloidosis (mean age, 59.9+/-8.8 years) and controls with M-protein (MGUS controls, n=6) and without it (negative controls, n=9). The patients showed a significantly higher value in the serum predominant FLC:serum creatinine ratio (43.8+/-63.2) and CD38++ CD19- CD56+ subpopulation (monoclonal plasma cells) (2.57+/-5.35%) than either the negative (p<0.0005 and p<0.001, respectively) or MGUS controls (p<0.05). With respect to maturation of plasma cells in the bone marrow, the intermediate (MPC-1+ CD45- CD49e-) and mature (MPC-1+ CD45+ CD49e-) subtypes were significantly higher (49.2+/-23.2%, p<0.005) and lower (27.6+/-21.3%, p<0.005) in the patients than in the negative controls, respectively. The serum predominant FLC:serum creatinine ratio was elevated in parallel with an increase in CD38++ CD19- CD56+ and MPC-1+ CD45- CD49e- cells and a decrease in mature subtypes (MPC-1+ CD45+ CD49e- and MPC-1+ CD45+ CD49e+ cells), There was a significantly positive correlation between the serum predominant FLC:serum creatinine ratio and either CD38++ CD19- CD56+ (r=0.510, p<0.05) or MPC-1+ CD45- CD49e- cells (r=0.481, p<0.05). In primary AL amyloidosis M-protein is probably produced by increased monoclonal plasma cells in the bone marrow, particularly by the intermediate subpopulation with a phenotype of MPC-1+ CD45- CD49e-.