Dendritic cells (DC) pulsed with multiple myeloma (MM) patient-specific idiotype (Id) protein can induce MM-specific T-cell responses. We established serum-free culture conditions to generate monocyte-derived DC for clinical use to circumvent anti-xenogenic immune responses with repetitive vaccinations. In a clinical phase I trial twelve patients responsive to high dose chemotherapy (HDT) were vaccinated with autologous Id pulsed DC vaccines followed by Id/keyhole limpet hemocyanin (Id/KLH) booster immunizations co-injected with granulocyte-macrophage colony-stimulating factor as adjuvant. In vitro studies showed that serum-free-generated DC were equally effective in the induction of specific T-cell responses as were DC generated with fetal calf serum. On average 4.5 x 10 (6) DC of> 60% purity were generated from peripheral blood monocytes obtained 3-6 months after HDT and autologous stem cell transplantation. Ten of twelve patients received all planned vaccines without serious toxicity. Two patients developed Id-specific T-cell proliferative responses, in one patient an Id-specific cytotoxic T lymphocyte (CTL) response was measured. Id-specific TH1 cytokine secretion was found in one of the T-cell responding patients. All patients who received at least three Id/KLH vaccines mounted strong KLH specific T-cell and delayed antibody responses. Two patients remain in clinical partial response at 25 and 29 months after the start of the vaccination and ten patients have progressed, six of whom have died from progressive disease or infectious complications. Serum-free DC vaccines induce Id-specific T-cell responses in MM patients.