We report a case of IgG-kappa multiple myeloma associated with neutrophilia (WBC 31,300/microl, neutrophil 90.5%). Interestingly, the serum level of granulocyte colony stimulating factor (G-CSF) in this patient was elevated to 1,500 pg/ml (normal range: 5.78-27.5). Plasma cells were 35% in the bone marrow and were strongly stained with anti-G-CSF antibody. To directly study the production of G-CSF from plasma cells in this patient, CD138 positive plasma cells were purified from bone marrow of multiple myeloma patients by magnetic sorting. The expression of G-CSF mRNA was observed in CD138 positive plasma cells from this myeloma patient with neutrophilia by RT-PCR. In contrast, the expression of G-CSF mRNA was not detected in CD138 positive plasma cells from the other multiple myeloma patients without neutrophilia and 4 human myeloma cell lines (HS-Sultan, IM9, RPMI8226, U266) by RT-PCR. After the CD138 positive plasma cells were cultured in vitro for 48 h, the production of G-CSF protein was confirmed (71.8 pg/ml) in the supernatant by ELISA. These results indicated plasma cells of this myeloma patient directly produced G-CSF and that this was the primary cause of neutrophilia.