The aim of the present study was to determine whether activin A concentrations are dependent on feto–placental oxygen availability and to investigate the temporal relationship of activin A with prostaglandin (PG) E₂ and cortisol. Nine fetal sheep (six hypoxic and three control) were instrumented and catheterised at 0.8 gestation. Reduced uterine blood flow was used to achieve three levels of hypoxia (mild = fetal SaO₂ 40–50%; moderate = fetal SaO₂ 30–40%; severe = fetal SaO₂ 20–30%), for 4 h on 3 consecutive days. Activin A, PGE₂ and cortisol levels were determined in maternal and fetal blood and amniotic fluid. Moderate and severe hypoxia produced a significant (P < 0.05) increase in fetal plasma activin A concentrations. The amniotic fluid activin A concentrations were 15-fold higher than those in the fetal circulation, but were unchanged by hypoxia. The fetal PGE₂ response reflected the degree of hypoxia over the 3 days, with moderate and severe hypoxia producing a significant (P < 0.05) increase in PGE₂ concentrations. Fetal plasma cortisol concentrations were increased (P < 0.05) during all levels of hypoxia. Fetal arterial activin A was increased in response to moderate and severe hypoxia, but levels were not maintained over the hypoxic period. The increases in activin A and cortisol concentrations preceded the increase in PGE₂.