Antimicrobial peptides play an important role in the innate immune response. Deficiency in salivary LL-37 antimicrobial peptide has been implicated in periodontitis in patients with morbus Kostman syndrome. Down syndrome is associated with periodontitis, diminished salivary flow, and salivary immunoglobulin deficiency. In the present study, levels of LL-37 and its hCAP18 precursor were measured in saliva samples from young individuals with Down syndrome and compared with levels in those from age-matched healthy controls. LL-37 and human cathelicidin antimicrobial protein (hCAP18) were detected in whole but not in parotid saliva. hCAP18 was more abundant than LL-37. The concentrations of salivary hCAP18 and LL-37 were found to be higher in individuals with Down syndrome than in healthy controls, but their secretion rates were similar. We concluded that, while the adaptive immunity of individuals with Down syndrome is impaired at the oral mucosa, the secretion rate of the LL-37 component of the innate immune system is normal.