The monocyte/macrophage cell lineage is an essential component of host defense. Functional deficiencies have been described in neonatal monocytes, but knowledge of membrane antigen and receptor ligand expression in neonatal monocytes is incomplete. In this study, antigen and receptor ligand expression of cord blood monocytes (CBM) was examined and compared to adult peripheral blood monocytes (PBM). Leu-M3 and Leu-M5 antigens were shown to be present on all CBM. Using dual fluorescence microfluorometry, the percentage and intensity of expression of HLA-DR, CD4 antigens, Fcγ and IL-2 receptors (IL-2R) on Leu-M3⁺ and Leu-M5⁺ CBM were compared to PBM. A lower percentage of expression of HLA-DR⁺ (87 ± 3% vs. 95 ± 1%, p = 0.02) and FCγRII⁺ (96 ± 1% vs. 99 ± 0.2%, p = 0.04) was noted on CBM. CD4, FCγRI, and FCγRIII expression on CBM were comparable to PBM. LPS stimulation of CBM induced IL-2R expression and enhanced HLA-DR antigen expression as seen previously on PBM. These findings indicate that CBM are phenotypically comparable to adult PBM with deficiencies localized only to a few specific areas.