We recently showed that endometrial tissue produces hCG during the secretory phase of the menstrual cycle. Based on these findings, we hypothesized that the decidua should also be able to secrete hCG. We examined the decidualized endometrium of patients with extrauterine pregnancies. Decidual specimens were obtained for mRNA extraction and paraffin embedding from 24 patients that were between weeks 6-11 of tubal pregnancy. Tissues were evaluated and classified into one of three groups based on the endometrial differentiation that took place prior to conception: (A) high secretory transformation, (B) diminished transformation with restricted decidualization and (C) inferior endometrial proliferation. Decidual gland hCG secretion was demonstrated immunohistochemically and by Western blotting. Serum hCG levels were higher (P < 0.0001) in patients from group A than group C. mRNA expression of both the beta subunit (beta-hCG) and alpha subunit (alpha-CG) was determined by RT-PCR. Furthermore, the specificity of beta-hCG amplification was confirmed by restriction enzymes. beta-LH amplification was not found. Moreover, the degree of endometrial transformation and the level of decidualization was found to correlate with hCG hormone staining and beta-hCG mRNA expression. hCG protein in the decidua was present in the glands of the compact layer and in the spongy layer, and was more pronounced in previously transformed high secretory endometrium than in inferior endometrium. In conclusion, this study provides the first evidence that hCG is produced in the decidua of patients during extrauterine pregnancies and might play a possible paracrine role.