OBJECTIVE We examined uterine tissue samples obtained from premenopausal women with uterine leiomyoma treated with gonadotropin-releasing hormone agonist (GnRHa) to investigate the mechanism of the effects of GnRHa. METHODS Surgically resected myoma tissue obtained from 26 premenopausal patients with uterine leiomyoma treated with GnRHa, 20 premenopausal patients with uterine leiomyoma who did not receive GnRHa treatment, and 15 postmenopausal women with uterine leiomyoma were examined histologically. RESULTS GnRHa treatment reduced the size of uterine leiomyomata and induced significant hyaline degeneration in tumor tissue. Le(Y)-antigen expression was detected in 18 (69.3%) of 26 GnRHa-treated patients (P < 0.02) and in 12 (80.0%) of 15 postmenopausal women (P < 0.05), but in only eight (40.0%) of the 20 premenopausal patients who did not receive GnRHa. Apoptotic cells, detected by the nick-end labeling method were observed in 14 patients (53.8%) in the GnRHa-treated group, 10 patients (50.0%) in the non-treated group, and 12 postmenopausal women (80.0%). CONCLUSIONS Our findings suggest that induction of apoptosis may be a mechanism of the effect of GnRHa in leiomyoma.