The study aim was to determine whether prostaglandin E(2) (PGE(2)) in gingival crevicular fluid (GCF) could serve as a risk factor for periodontitis in human immunodeficiency virus-positive (HIV(+)) patients. Clinical measurements, including gingival index (GI), plaque index, bleeding index, probing depth (PD), attachment loss (AL) and GCF samples were taken from two healthy sites (including sites with gingival recession, GI=0; PD< or =3 mm; AL< or =2 mm), three gingivitis sites (GI>0; PD< or =3 mm; AL=0) and three periodontitis sites (GI>0; PD> or =5 mm; AL> or =3 mm) of each of the 30 patients at baseline and 6-month visits. GCF samples were also taken by means of paper strips. GCF PGE(2) levels were determined by a sandwich ELISA. The progressing site was defined as a site which had 2 mm or more attachment loss during the 6-month study period. The mean amounts of PGE(2) were significantly higher in gingivitis and periodontitis sites than in healthy sites (p<0.0001). GCF levels of PGE(2) were significantly correlated with probing depth, attachment loss, CD4(+) cells, viral load, age and smoking pack-years at baseline and 6-month visits (0.0001<p<0.05). Repeated measures analysis of 19 active sites versus 221 inactive sites indicated that PGE(2) levels were significantly higher in active sites than in inactive sites (p<0.0001). It is likely that the compromised immune system contributes to the pathogenesis of periodontitis in HIV(+) patients. It is well known that the activated inflammatory cells produce inflammatory mediators which stimulate the production of PGE(2). Longitudinal evaluation of GCF PGE(2) with respect to the progression of untreated periodontitis sites in HIV(+) subjects will contribute to the understanding of the pathogenesis of periodontitis in HIV(+) patients. These data indicate that sites with high GCF levels of PGE(2) in HIV(+) patients are at significantly greater risk for progression of periodontitis.