In this study, we re-visited the issue of hyper-responsiveness of monocytes to bacterial lipopolysaccharide (LPS) in aggressive periodontitis patients. We used whole-blood cultures to compare monocyte activation by Porphyromonas gingivalis LPS between Thai subjects with generalized aggressive periodontitis and those without periodontitis. Upon stimulation with P. gingivalis LPS, expression of co-stimulatory molecules on monocytes and expression of CD69 on NK and gamma delta T-cells were analyzed by flow cytometry, and the production of interleukin-1 beta and prostaglandin E(2) was monitored by ELISA. LPS stimulation resulted in a dose-dependent up-regulation of CD40, CD80, and CD86 on monocytes, and up-regulation of CD69 on NK cells and gamma delta T-cells in both the periodontitis and non-periodontitis groups. The levels of activation markers and the mediator production after LPS stimulation were quite similar for both groups. In conclusion, we did not observe hyper-responsiveness of monocytes to P. gingivalis LPS challenge in Thai patients with aggressive periodontitis.