Idiotypic protein (Id) produced by myeloma cells is clonespecific and may be a suitable tumor-specific antigen for immune targeting. Advances in dendritic cell (DC) technology suggest the opportunity for using this potent antigen presentation system to deliver myeloma Id to the autologous host to elicit anti-tumor immune responses. We have generated DCs from adherent PBMCs from 6 patients with IgG myeloma. These cells were pulsed with the autologous Id and a control vaccine, KLH, and re-infused i.v. back to the patients on 3 separate occasions. Immune responses to KLH and autologous Id were measured and clinical responses monitored. We found that all treatments were well tolerated without any side effects. All patients developed both B-and T-cell responses to KLH, suggesting the integrity of the host immune system to mount immune responses to an antigen delivered using our vaccination strategy. Id-specific responses were also observed. PBMC proliferative responses to Id were observed in 5 of the 6 patients following treatment. In 2 patients, the responses were associated with the production of IFN-โฅ. There were also increases in cytotoxic T-cell precursor frequencies for Id-pulsed autologous targets in 3 patients. B-cell responses characterized by the production of anti-Id IgM occurred in 3 and anti-Id IgG in 4 of the 5 evaluated patients. In 1 patient, a modest (25%) but consistent drop in the serum Id level was observed. Id-pulsed DC vaccination can therefore elicit potentially useful antimyeloma immune responses in patients with multiple myeloma.