Neonatal immune responses have been associated with the development of atopy in childhood. We assessed in cord blood mononuclear cells (CBMC) whether increased allergen/mitogen-induced lymphoproliferation (LP) is associated with pro-allergic Th2 cytokine IL-13 or Th1 cytokine IFN-gamma secretion. We determined whether LP to one allergen is related to heightened lymphocyte function to other allergens/mitogen. CBMC from 135 neonates were stimulated with house dust mite (Derf1), cockroach, ovalbumin, or mitogen. LP to one allergen was associated with significantly increased LP to other allergens/mitogen. Increased Derf1-LP was associated with increased Derf1-induced IL-13 secretion (r = 0.21, p = 0.01). After adjusting for neonatal gender, race, and maternal smoking, Derf1-LP remained associated with Derf1-IL-13 (OR 3.08, 95% CI 1.56-6.10). Increased mitogen-induced proliferation was associated with increased mitogen-induced IL-13 secretion (r = 0.37, p < 0.001). For some individuals, a predisposition to a heightened immune response is already evident at birth. Whether this phenotype results in atopy in childhood warrants further investigation.