L-Arginine transport by the fetal side of human placenta was investigated through the characterization of L-[3H]arginine uptake in isolated perfused cotyledon. Competitive inhibition experiments suggest the presence of at least two transport systems: a Na+-independent, pH-insensitive system inhibitable by cationic amino acids, similar to system y+, and a Na+-dependent system which recognizes both cationic and neutral amino acids only in the presence of Na+, i.e. a Bo,+-like system. The kinetic analysis of L-arginine uptake in the presence of Na+ revealed that the process is mediated by saturable components: a high-affinity system (Km = 167 ± 18·0 μM; Vmax = 0·174 ± 0·012 μmol min-1) and a low-affinity carrier (Km = 980 ± 112 μM; Vmax = 1·60 ± 0·12 μmol min-1). In the absence of Na+, L-arginine uptake was fitted by one model with a Michaelis-Menten constant of 200 ± 24·8 μM. These results suggest that the high-affinity component corresponds to the Na+-independent system y+, whilst the low-affinity system may represent the activity of the Na+-dependent Bo,+ transporter. Kinetic studies in placentae taken from aspirin-treated pregnancies showed that L-arginine is transported with a significantly higher affinity (Km = 42·5 ± 5·7 μM), but with a lower capacity (Vmax = 0·064 ± 0·003 μmol min-1) than in the non-treated group. The latter finding suggests that aspirin would facilitate the uptake of the NO precursor only at very low arginine concentrations.