Interleukin-1 (IL1) is believed to play a central role in the immuno-inflammatory process associated with endometriosis. IL1 triggers cell activation via its receptor type I (IL1R1), but its receptor type II (IL1R2) is known instead as a scavenger that buffers the cytokine's effects. Our previous studies have shown increased expression of IL1R1 in active endometriotic implants compared to normal and endometriosis women-derived endometrial tissues, and a simultaneous decrease in IL1R2 expression at the protein level. In the present study, in situ hybridization demonstrated a noticeable decrease in IL1R2 mRNA hybridization score in eutopic and matched ectopic endometrial tissues of women with endometriosis compared to normal women in the stroma (P<0.001 and P<0.001, respectively) and the epithelium (P<0.01 and P<0.05, respectively), whereas IL1R1 mRNA hybridization score was higher only in the ectopic implants, with a statistically significant difference in the stroma (P<0.05). This was corroborated by RT-PCR analysis of IL1R1 and IL1R2 mRNAs in ectopic (P<0.05 and P<0.05, respectively) and matched eutopic (P=0.22 and P<0.05, respectively) endometrial tissues from women with endometriosis compared to endometrial tissues from normal women. The decrease in IL1R2 mRNA levels in eutopic endometrial tissue of endometriosis women, and the concomitant increase in IL1R1 mRNA levels in ectopic implants, reveal a profound defect in IL1R 1 and IL1R2 gene expression which may accentuate the capability of this tissue to respond to IL1 and favor its ectopic growth.