We evaluated the role of the immune system in the pathogenesis of the periprosthetic capsular contracture, the most frequently occurring complication following the implant of silicone prostheses. Peripheral blood samples from 22 patients with silicone-gel-filled implants were examined. In all cases a capsule was felt by palpation, and it was classified according to the Baker scale. Ten patients (group 1) had a Baker 2 contracture, and 12 (group 2) had severe contracture rated 3 and 4. The cells positive to antigens CD3, CD4, CD8, HLA-DR, CD19, CD25, CD57, CD16, and CD14, and the cytotoxic activity of the lymphocytes on target cells K562 were assessed by cytofluorimetric analysis. At time 0 there were no statistically significant differences between patients and normal subjects, nor between the two groups. At 48 h, the group 2 patients had a number/mm3 of cells CD57 + significantly higher than both group 1 and control group (P < .05). In group 1 patients, the cytotoxic activity was similar to that of normal subjects, whereas in group 2 it was significantly increased, in respect to both the controls (P < .05) and group 1 (P < .001). In all groups, the contact of the lymphocytes with the silicone extract did not modify either the antigen expression or the lymphocyte functional activity. On the basis of these results we hypothesize the involvement of the immune system in the formation of the capsular contracture around the prosthesis.