Objective: To investigate S100P expression and localization in human endometrium throughout the menstrual cycle. Design: Experimental study. Setting: University hospital. Patient(s): Eighty-four women. Intervention(s): Complementary DNA (cDNA) microarray analysis was performed on human endometrium from days LH+4, LH+7, and hCG+7. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to detect the expression of S100P and of additional S100 family members, S100A4, S100A13, and S100A6. Immunofluorescence was used to detect the localization of S100P protein in LH+7 and LH+4 endometrium. Main Outcome Measure(s): Differential gene expression, levels of S100P messenger RNA (mRNA), and protein expression and immunofluorescent localization of S100P. Result(s): A statistical method, based on hierarchical clustering, identified genes whose expression varied at LH+7 compared with LH+4. We found that S100P was the fourth most up-regulated gene at LH+7. The S100P mRNA and protein levels were quite low during the proliferative phase and LH+4, but were elevated significantly at LH+7. The S100P expression at hCG+7 was lower than that at LH+7. However, the expression of S100A4, S100A13, and S100A6 did not vary throughout the menstrual cycle. Conclusion(s): S100P was specifically up-regulated during the implantation window. The underlying biological effects of S100P need further exploration. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.