Dendritic cells were assayed repeatedly in the peripheral blood of consenting melanoma patients receiving adjuvant biotherapy for high risk (stages IIb-IV) melanoma. Postoperatively, adjuvant biotherapy consisted of granulocyte-macrophage colony-stimulating factor [125 microg/m2/day] for 14 consecutive days, followed by interleukin-2 [9 million IU/m2/day] for the next 4 days, and then no treatment for 10-12 days. This was repeated monthly for six cycles. Although white blood cell counts increased, there was no significant elevation in dendritic cell counts during therapy of eleven patients. Within the first cycle during granulocyte-macrophage colony-stimulating factor treatment of seven patients, the absolute DC count decreased (p < 0.04), the percentage of myeloid BDCA-1+ BDCA-2- dendritic cells was significantly lower than baseline (p < 0.003) and the percentage of plasmacytoid BDCA-1- BDCA-2+ dendritic cells was significantly higher than baseline (p < 0.009). Our data suggest mechanisms of potential anti-tumor responses in patients receiving systemic sequential granulocyte-macrophage colony-stimulating factor and interleukin-2 do not include a cumulative gain in peripheral dendritic cell counts or an increase in myeloid BDCA-1+ BDCA-2- dendritic cell subset in the peripheral blood.