The mRNA that encodes for NaPi-2, the renal Na(+)-Pi cotransporter that is upregulated by Pi depletion in the adult rat, is low in the young animal. Yet, renal Na-Pi cotransport rates are higher in rapidly growing than in fully grown rats. The aim of this study was to unravel the molecular basis of this apparent discrepancy. Poly(A) RNA obtained from the renal cortex of young animals induced higher rates of Na(+)-Pi cotransport in oocytes than equal amounts of poly(A) mRNA obtained from the renal cortex of mature rats. Moreover, poly(A) RNA obtained from renal cortex of rapidly growing animals treated with antisense NaPi-2 oligomers or depleted of NaPi-2 transcripts by subtractive hybridization with cDNA generated from the renal cortex of adult rats retained its ability to induce Na(+)-Pi cotransport in oocytes. In addition, renal poly(A) RNA of the young subjected to subtraction hybridization generated a 379-base pair reverse transcriptase-polymerase chain reaction product common to all known type II Na(+)-Pi cotransporters. These observations permit us to surmise that the high rates of Na(+)-Pi cotransport prevailing during growth are due, at least in part, to the expression of a specific mRNA that is only partially homologous to that of NaPi-2.