The production of IL-10 by newborns has not been studied in much detail. We analyzed the IL-10 production by, and surface marker distribution of, cord blood mononuclear cells (n = 47); adult peripheral blood mononuclear cells (n = 30) were used as controls. Both the baseline (0.79 versus 1.54 ng/mL, p = 0.001) and lipopolysaccharide-stimulated (1.20 versus 2.88 ng/mL, p = 0.003) levels of IL-10 production were significantly lower in newborns than in adults. No significant differences were observed after stimulation with concanavalin A. Both cord blood and adult CD19(+)CD5(+) cells were able to produce IL-10; however, the level of production was only an average of 16% of the total stimulated IL-10 production by unfractionated cells, indicating that CD5(+) B cells are not the primary source of IL-10 in either adults or newborns. In newborns, the proportion of naive CD4(+)CD45RA(+) cells was inversely correlated with IL-10 response to lipopolysaccharide (r = -0.49, p = 0.004) indicating a role for maturing T cells in neonatal IL-10 production; the number of macrophages was not significantly correlated with IL-10 response (r = 0.30, p = 0.10). In contrast, in adults IL-10 production correlated with the number of macrophages (r = 0.49, p = 0.01) but not CD4(+)CD45RA(+) cells (r = -0.06, p = 0.77). We conclude that newborns produce less IL-10 than adults; the primary cells of origin and the regulatory mechanisms may be different from those observed in adults.