The objective of this study was to determine the phenotypic profile of blood mononuclear cells, specifically CD8(+)/CD28(+) cells, in patients with generalized aggressive periodontitis (GAgP) and chronic periodontitis (CP) in peripheral blood and in blood obtained from periodontal defect site which might contribute to tissue damage. 13 GAgP, 11 chronic periodontitis (CP) and 5 healthy controls (H) were included in the study. Plaque index (PI), bleeding on probing (BoP), periodontal probing depth (PPD) and clinical attachment level (CAL) were recorded. Blood from the base of periodontal defect site and peripheral blood from the antecubital vein were obtained. Relative counts of CD45(+), CD3(+), CD4(+), CD8(+)/CD28(+), CD8(+)/CD28-, CD19(+), CD16(+)/CD56(+)/CD3, CD3(+)/CD16(+)/CD56(+) receptors were determined with two color flow cytometry using monoclonal antibodies. BoP, PPD and CAL were significantly higher in both periodontitis groups than healthy controls (p < 0.05). Activated cytotoxic T cells, CD8(+)/CD28(+) cells, were significantly elevated in GAgP and CP groups compared to HC both in blood obtained from defect site and blood obtained from systemic circulation (p < 0.05). GAgP and CP patients have an increased levels of activated cytotoxic T cells as a result of inflammation which may cause severe tissue damage that lead to severe and rapid loss of periodontal tissues.