Objective: To test the feasibility of ProteinChip (Ciphergen Biosystems, Inc., Fremont, CA) technology as a proteomic tool in discovering and identifying proteins that are differentially expressed in endometrium, endometriotic tissue, and normal peritoneum from women with and without endometriosis. Design: Differential analysis of protein expression in women with and without endometriosis. Setting: University hospital. Patient(s): A total of nine patients during their secretory phase (days 20- 22) were selected for this study on the basis of cycle phase and presence/or absence of endometriosis. Intervention(s): Twelve tissues used in the study included six endometrial biopsies from women with mild endometriosis (n = 3) and a normal pelvis (n = 3) as well as paired samples of peritoneal endometriotic lesions (n = 3) and macroscopically normal peritoneum biopsies (n = 3) from three women with endometriosis. Main Outcome Measure(s): Numerous expression differences were observed in the above comparisons, representing both up-regulation and down-regulation in protein and peptide expression levels. Result(s): Endometrial expression for a number of proteins and peptides in the range of 2.8- 12.3 kDa was 3- 24 times lower in women with endometriosis than in those without endometriosis. When compared with normal peritoneum, endometriotic lesions showed an increased expression for a set of proteins and peptides in the range of 3- 96 kDa, and especially an up-regulated cluster of proteins between 22 and 23 kDa, identified to be transgelin, a smooth muscle actin-binding protein. Conclusion(s): This preliminary study demonstrated that differential protein profiling by using ProteinChip array technology is feasible, reproducible, and may be developed into a powerful tool for endometriosis research. Objective: To test the feasibility of ProteinChip (Ciphergen Biosystems, Inc., Fremont, CA) technology as a proteomic tool in discovering and identifying proteins that are differentially expressed in endometrium, endometriotic tissue, and normal peritoneum from women with and without endometriosis. Design : Differential analysis of protein expression in women with and without endometriosis. Setting: University hospital. Patient (s): A total of nine patients during their secretory phase (days 20-22) were selected for this study on the basis of cycle phase and presence / or absence of endometriosis. Intervention (s): Twelve tissues used in the study included six endometrial biopsies from women with mild endometriosis (n = 3) and a normal pelvis (n = 3) as well as paired samples of peritoneal endometriotic lesions (n = 3) and macroscopically normal peritoneum biopsies (n = 3) from three women with endometriosis. Main Outcome Measure (s): Numerous expression differences were observed in the abo ve comparisons, representing both up-regulation and down-regulation in protein and peptide expression levels. Result (s): Endometrial expression for a number of proteins and peptides in the range of 2.8-12.3 kDa was 3- 24 times lower in women with Endometriosis than in those without endometriosis. When compared with normal peritoneum, endometriotic lesions showed an increased expression for a set of proteins and peptides in the range of 3-96 kDa, and especially an up-regulated cluster of proteins between 22 and 23 kDa, Conclusion (s): This preliminary study demonstrated that differential protein profiling by using ProteinChip array technology is feasible, reproducible, and may developed into a powerful tool for endometriosis research.