The aim of the present study was to evaluate whether spontaneous labor at term and pathological preterm labor are associated with changes in the expression of activin A and activin receptor mRNAs in fetal membranes. In addition, amniotic fluid activin A concentration in women delivering at term or undergoing preterm labor was also measured. The expression of activin beta A subunit and activin receptor type II and type IIB mRNAs was assessed by reverse transcriptase-PCR on specimens of amnion and chorion collected from patients delivering at term or undergoing preterm labor. Control specimens were collected from women delivered by elective cesarean section who had not experienced labor. A specific two-site ELISA was used to measure activin A concentrations in the amniotic fluid. A cross-sectional study of amniotic fluid retrieved by amniocentesis from 109 pregnant women was carried out. Patients were classified into the following groups: (1) healthy controls at term but not in labor (n = 25); (2) healthy controls at term in spontaneous labor (n = 40); (3) healthy controls between 23 and 36 weeks of gestation (n = 12); (4) patients in preterm labor responding to tocolytic treatment (n = 19); (5) patients in preterm labor with subsequent delivery (n = 13). Activin beta A subunit and activin receptor type IIB mRNA levels in both the chorion and amnion in women delivering at term or after preterm labor were significantly higher than in women delivering without undergoing labor (P < 0.01). Expression of activin receptor type II mRNA in membranes did not differ among the three groups of women. Amniotic fluid activin A concentration in patients in labor was significantly higher than in those at term but not in labor (P < 0.01). Patients in preterm labor had significantly higher amniotic fluid activin A concentrations than women at the same stage of gestation (P < 0.01). The highest values were found in women undergoing preterm labor and subsequent delivery. In conclusion, spontaneous labor and preterm labor are characterized by increased synthesis and release of activin A from amniotic and chorionic cells and by an augmented expression of activin type IIB receptor.