Cord blood (CB) transplantations are associated with low graft-versus-host disease (GVHD). The pathophysiology of GVHD involves interaction and activation of different cell types, as lymphocytes and monocytes, and results in a cascade of cytokine production. After antigen or mitogen stimulation, CB monocytes release lower levels of cytokines than adult blood (AB) monocytes. In this study, the detection of intracellular IL-1β and TNF-α produced by monocytes was evaluated in response to tuberculin PPD to investigate whether the reduced capacity of CB monocytes to secrete cytokines could be related to an impaired functional activity and to a particular phenotypic profile. Results showed that the percentage of CD64+ monocytes producing intracellular IL-1β and TNF-α was significantly lower in CB and that the phenotypic profile of CB monocytes producing these cytokine (CD64+ CD14+) was different to that of AB monocytes (CD64+ CD14+, CD64+ CD33+ and CD64+ CD45RO+). These results suggest that the lower capacity of CB monocyte populations to produce IL-1β and TNF-α might be due to a functional immaturity of CB monocytes at the cellular level as reflected by the different phenotypic profile of CB monocytes. Bone Marrow Transplantation (2001) 27, 1081–1086.