A protein that copurifies with the bovine prostaglandin F2alpha (FP) receptor has been isolated and the corresponding rat cDNA has been cloned. Transfection experiments suggest that this protein inhibits binding of [3H]prostaglandin F2alpha ([3H]PGF2alpha) to FP. Histologically, this protein (FP regulatory protein or FPRP) shows a distribution coinciding well with those cells and tissues that respond to PGF2alpha. A portion of the 3' untranslated region of the human homolog to fprp was subcloned, sequenced, and oligonucleotide primers chosen that allow polymerase chain reaction (PCR) amplification specifically of the human fprp sequence. These primers were then used in a PCR-based mapping-protocol. The human fprp gene was first socalized through human/rodent somatic cell hybrids to human chromosome 1 (100% concordance), and further through yeast artificial chromosome (YAC) pools to region 1p13.1-q21.3 (level 1 mapping). In view of the specific histologic localization of this negative regulator, possible pathological conditions are mentioned that may cosegrepate with this chromosomal region.