To estimate regulatory cytokine synthesis and lymphocyte activation in the peripheral blood and endometrial tissue of patients with endometriosis. Design: Controlled clinical study. Setting: Medical center. Patient(s): Fifteen women with laparoscopically diagnosed endometriosis; 20 gynecologically healthy women with previously documented fertility (control group). Intervention(s): Peripheral venous blood sampling; laparoscopic collection of ectopic and matched eutopic endometrium. Main Outcome Measure(s): Messenger RNA (mRNA) for interleukin (IL)- 2, IL- 4, and IL- 10 expression in peripheral and endometrium lymphocyteMs was assessed by real-time reverse transcriptase polymerase chain reaction; intracellular synthesis of these cytokines and lymphocyte phenotype profile were established by flow cytometry. Result(s): Both mRNA expression and intracellular synthesis of IL- 4 and IL- 10 were sharply increased in peripheral lymphocytes. The same changes were observed for IL- 4 in ectopic endometrium of women with endometriosis. Simultaneously, elevation of the amount of pan- B cells, CD20+ CD5+ B- 1 cells, and activated HLA- DR+ CD20+ B lymphocytes was observed in endometriosis lesions. Only an enhanced amount of B lymphocytes was seen in eutopic endometrium. Conclusion(s): Endometriosis development is accompanied by the activation of a T- helper type 2 immune response at the systemic and local levels. Our results support the hypothesis regarding the autoimmune nature of endometriosis and can explain the high level of autoantibody production in patients with endometriosis. To estimate regulatory cytokine synthesis and lymphocyte activation in the peripheral blood and endometrial tissue of patients with endometriosis. Design: Controlled clinical study. Setting: Medical center. Patient (s): Fifteen women with laparoscopically diagnosed endometriosis; 20 gynecologically healthy women with previously documented Intervention (s): Peripheral venous blood sampling; laparoscopic collection of ectopic and matched eutopic endometrium. Main Outcome Measure (s): Messenger RNA (mRNA) for interleukin (IL) IL-10 expression in peripheral and endometrium lymphocyte MS was assessed by real-time reverse transcriptase polymerase chain reaction; intracellular synthesis of these cytokines and lymphocyte phenotype profiles by established flow cytometry. Results (s): Both mRNA expression and intracellular synthesis of IL- 4 and IL-10 were sharply increased in peripheral lymphocytes. The same changes were observed for IL-4 in ectopic en Dometrium of women with endometriosis. Simultaneously, elevation of the amount of pan-B cells, CD20 + CD5 + B- 1 cells, and activated HLA- DR + CD20 + B lymphocytes was observed in endometriosis lesions. Only an enhanced amount of B lymphocytes was seen in eutopic Conclusion (s): Endometriosis development is accompanied by the activation of a T- helper type 2 immune response at the systemic and local levels. Our results support the hypothesis regarding the autoimmune nature of endometriosis and can explain the high level of autoantibody production in patients with endometriosis.