The objective of the present study was to evaluate the cyclic changes and regional localization of immunoreactive c-fos and prolactin (PRL) in the human endometrium, using immunohistochemistry. Immunoreactive PRL was found in the epithelium of 9.1% of the proliferative specimens and in 55.6% of the secretory specimens (p < 0.05, Fisher's exact test). In the endometrial stroma, immunoreactive PRL was present in 9.1 and 66.7% of the proliferative and secretory samples, respectively (p < 0.01). Immunoreactive c-fos predominated in the stroma and was identified in 54.5% of the specimens in the proliferative phase, but in only 7.1% of those in the secretory phase (p < 0.05). The progesterone/estradiol ratio was lower in the patients expressing immunoreactive c-fos (median = 13.1 ng/ml) compared to those who did not (median = 84.5 ng/ml, p < 0.05). We conclude that immunoreactive c-fos is found mostly in stromal cells during the proliferative phase of the menstrual cycle, and is sharply reduced during the secretory phase, when the endometrium is under progesterone stimulation - attested by PRL production.