Patients with advanced squamous cell carcinomas of the head and neck (SCCHN) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells that play a role in antitumor immune responses. Using multicolor flow cytometry, the percentages of lineage-negative (LIN(-)) and DR(+) DC precursors, as well as their LIN(-)DR(+)CD11c(+) (myeloid) and LIN(-)DR(+)CD123(+) (lymphoid) subsets, were determined in the peripheral blood of 36 patients with SCCHN before surgery. Peripheral blood mononuclear cells of 28 age- and sex-matched healthy individuals were used as controls. The proportions of LIN(-)DR(+) cells were found to be comparable in the circulation of patients and controls. However, the relative level of DR expression in LIN(-)DR(+) DC was lower in patients than in controls, suggesting a difference in the maturity of DC. The relative proportion of LIN(-)DR(+)CD123(+) cells in the LIN(-)DR(+) subset of DC did not differ significantly in patients compared with normal individuals. However, the percentage of myeloid-derived LIN(-)DR(+)CD11c(+) DCs was significantly lower (P < 0.002) in SCCHN patients than in controls. Of the 13 patients who were restudied 6 weeks after surgery, 9 showed an increase of the myeloid-derived LIN(-)DR(+)CD11c(+) DC subset postoperatively. This observation suggests that deficiency in the myeloid-derived DC precursors in patients with SCCHN is related to the presence of tumor and is reversible. An overall decrease in the myeloid-derived subset of DC could contribute to the failure of SCCHN patients to develop effective antitumor immune responses.