Metabolism of prostaglandin F2 alpha (PGF2 alpha) was studied with both qualitative and quantitative techniques in liver, kidney and lung of fetal and maternal guinea pigs at term. In the pregnant guinea pigs 15-hydroxyprostaglandin dehydrogenase (PGDH) activities were highest in the kidney, followed by the lung and then by the liver. In fetuses PGDH activity was highest in the liver, followed in decreasing order by kidney and lung. The kidneys and lungs of the mothers showed a 6- to 10-fold higher PGDH activity than those of the litter (P less than 0.005), but the mean PGDH activity of liver was lower in the mothers than in the fetuses. It is suggested that the liver may play a major role in prostaglandin metabolism during fetal life, and may fulfil part of the function reserved to the lung during adult life. Maternal and fetal lungs differed greatly in their handling of PGF2 alpha. This was not due to a difference in aeration, for the differences in the metabolism of PGF2 alpha between mother and litter increased when well-aerated neonatal lungs were considered instead of non-aerated fetal lungs. The observed differences in enzyme activity between fetal and neonatal lungs add yet another dimension to the role of prostaglandins in the establishment of neonatal respiration.