The aim was to study the levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and matrix metalloproteinase-9 (MMP-9) in gingival crevicular fluid (GCF) from Down syndrome patients exhibiting gingival inflammation. The levels of PGE2, LTB4, and MMP-9 were determined in GCF from 18 Down syndrome patients and from 14 controls matched with respect to age and degree of gingival inflammation. Probing depth (PD) and gingival inflammation, assessed by bleeding on probing (BOP), were determined around all teeth. In each patient, GCF was collected from 6 sites (16m, 26m, 36m, 46m, 41m, 11d) using periopaper, and the volume was determined using Peritron 8000. The PGE2 and LTB4 levels were determined using RIA kits and MMP-9 level using ELISA kits. The degree of gingival inflammation, expressed as mean value of BOP (%) as well as the volume of GCF, was similar between Down syndrome patients and controls. The mean levels of PGE2, LTB4, and MMP-9 were significantly (P<0.05) higher in GCF from Down syndrome patients compared to controls. When comparing the two groups, the correlation coefficients for LTB4 to BOP and PD, respectively, as well as for MMP-9 to BOP significantly differed between Down syndrome and controls (P<0.05). The study supports the concept of an altered host response in periodontal tissue in Down syndrome subjects.