Asthma and type I diabetes are major causes of chronic illness in childhood which, according to the current paradigm, have mutually antagonistic immunopathologies. Nonetheless, the disorders appear to preferably coexist both on population and individual levels. To assess whether children with asthma and type I diabetes might have a common immunoregulatory defect. The spontaneous and anti-CD3+ anti-CD28-stimulated cytokine production patterns by peripheral blood mononuclear cells of 13 children with both asthma and diabetes, nine children with diabetes, 11 children with asthma and nine healthy children were assessed using cytometric bead assay. The spontaneous production of IFN-γ, TNF-α and IL-10 by mononuclear cells in children with both asthma and diabetes was elevated compared to the other study groups (p = 0.02, p = 0.001 and p = 0.04, respectively). Stimulation in vitro increased IL-10 secretion in solely diabetic (p = 0.008), asthmatic (p = 0.008) and healthy children (p = 0.01), but not in children with both diseases (p = 0.22). Children suffering from both diabetes and asthma display a unique cytokine secretion pattern, distinct from those of solely diabetic, asthmatic and healthy children. In particular, these children appear to have a defect in regulation of IL-10 secretion.