Objective: To investigate spontaneous endometrial apoptosis in women with unexplained infertility and to find out whether there is a possible relationship between endometrial apoptosis, age, and hormonal parameters. Study design: This study was designed as a prospective, case-controlled study in a University Hospital setting. A total of 34 endometrial biopsies were performed from 17 women with unexplained infertility and 17 fertile controls, who were admitted for tubal ligation. Endometrium was sampled on the seventh post-ovulatory day. On the same day of endometrial sampling, serum levels of FSH, LH, PRL, TSH, E2, progesterone, 17α-hydroxyprogesterone, testosterone and DHEA-S were determined. Endometrial glandular and stromal apoptosis were investigated by DNA nick end labeling (TUNEL) method on each sample. Endometrial apoptotic index was calculated and correlated with age and hormonal parameters. Results: There was no difference in either endometrial glandular apoptotic index (AI) or stromal AI between the groups. However, the mean glandular AI was significantly higher than the mean stromal AI (p = 0.0001). There was a strong correlation between endometrial AI and age (r = 0.91, p = 0.02). Serum T levels were significantly found to be decreased in the unexplained infertility group (p = 0.0001). In addition, serum TSH levels were positively correlated with AI in the glandular endometrium in women with unexplained infertility (r = 0.611, p = 0.009) Conclusion: Endometrial apoptosis increases with age. Serum levels of testosterone were lower in unexplained infertility. The effect of serum TSH levels on apoptosis in the glandular epithelium of the endometrium needs further studies. © 2005 Elsevier Ireland Ltd. All rights reserved.