OBJECTIVE Four-color multiparameter immunophenotyping has recently proven to be an attractive technique for evaluating the plasma cell (PC) compartment since it allows discrimination between myelomatous and normal PC. This study was designed to investigate: i) whether peripheral blood is less contaminated than bone marrow as a source for an autologous transplant; ii) the effect of growth factors on mobilizing myelomatous PC into peripheral blood; iii) the degree of contamination by myelomatous PC in apheresis samples; and iv) whether the number of PC increases during the last days of apheresis. METHODS Using 4-color antigen staining we investigated the composition of the PC compartment in 90 apheresis products from 40 patients with MM; in 17 cases bone marrow and peripheral blood samples were also simultaneously evaluated. RESULTS (i) All pre-mobilization bone marrow samples analyzed were always contaminated with myelomatous PC whereas only 41% of the post-mobilization peripheral blood samples were contaminated. Moreover, the use of peripheral blood would lead to a reduction of >5x10(5) infused myelomatous PC; (ii) mobilization with cytokines increased the number of circulating PC, generally because of an expansion of the normal PC population; (iii) forty-eight percent of all peripheral blood stem cell harvests were contaminated with myelomatous PC, although normal PC usually represented the predominant population; (iv) no significant changes were observed in the amount of contaminating myelomatous PC during the first three days of apheresis. CONCLUSIONS Multiparameter immunophenotyping is a useful approach for investigating the PC compartment in apheresis products.