The basis for the existence of a lower concentration of salicylate in the foetal than in the maternal blood was investigated in rats on day 20 of gestation. 2. Bolus injections of sodium salicylate were made into the mother and of [14C]-salicylic acid into its foetuses and serial maternal and foetal blood samples were collected. When derived on the basis of serum salicylic acid uncorrected for differences in ionization in the maternal and foetal blood, the placental clearance was 2.2 fold greater from the foetal to maternal side than that from the maternal to foetal side. 3. The greater foetal placental clearance relative to the maternal placental clearance was not due to any active placental transfer, since there was no evidence of saturation of this process and it was not affected by pretreatment with probenecid. Moreover, salicylic acid was not concentrated by placental slices in vitro and its placental uptake was not affected by dinitrophenol or by cooling. 4. Maternal blood pH was 0.19 units higher than the foetal blood pH. Administration of ammonium chloride or of sodium bicarbonate into the mother increased the foetal to maternal ratio of salicylic acid from 0.6 to approximately 1. 5. It is concluded that a foetal to maternal serum salicylate concentration-ratio of less than 1 simply reflects lower ionization in the foetus than in the mother, because foetal blood pH is lower than the maternal blood pH.
