Renal proximal Na/Pi-cotransport is increased in response to low dietary Pi intake. Recently, a cDNA (NaPi-2) related to the rat renal brush membrane Na/Pi-cotransporter has been cloned. In the present study, we used rats fed for 6 days with either a low Pi diet (LPD) or a high Pi diet (HPD), respectively. In parallel to an increased renal brush-border membrane Na/Pi-cotransport in LPD rats, there was also an increased content of NaPi-2 mRNA in renal cortex. After injection into Xenopus laevis oocytes, mRNA isolated from LPD rats induced a greater increase in Na/Pi-cotransport compared to mRNA from HPD rats. Hybrid depletion experiments suggested that mRNA-induced Na/Pi-cotransport is related to NaPi-2. We conclude that chronic Pi deprivation leads to an increased brush-border membrane Na/Pi-cotransport via an increase in the level of (NaPi-2) mRNA.