Both placental system A activity and fetal plasma cortisol concentrations are associated with intrauterine growth retardation but it is not known if these factors are mechanistically related. Previous functional studies using hepatoma cells and fibroblasts produced conflicting results regarding the regulation of system A by cortisol. Using the b30 BeWo choriocarcinoma cell line, we investigated the regulation of system A by cortisol. System A function was analysed using MeAIB transcellular transport studies. Transporter expression (SNAT1/2) was studied at the mRNA and protein levels using Northern and Western blotting respectively. Localisation was carried out using immunocytochemistry. The ¹⁴C-MeAIB transfer rate across BeWo monolayers following pre-incubation with cortisol for 24h was significantly increased compared to control. This was associated with a relocalisation of the SNAT2 transporter at lower cortisol levels and significant up regulation of mRNA and protein expression levels at cortisol levels greater than 1µM. This is the first study to show functional and molecular regulation of system A by cortisol in BeWo cells. It is also the first study to identify which system A isoform is regulated. These results suggest that cortisol may be involved in up-regulation of system A in the placenta to ensure sufficient amino acid supply to the developing fetus.