Recently, cloning of the gonadotropin-releasing hormone (GnRH) receptor from the human breast tumor cell line (MCF-7) and from an ovarian tumor, and its expression in various other human tumors, tumor cell lines and reproductive organs have been reported (Kakar et al., Mol. Cell. Endocrinol., 106 (1994) 145-149). In the present studies, we investigated the expression of GnRH and GnRH receptor mRNAs in normal human non-reproductive tissues. Using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques and specific oligonucleotide primers derived from the placental GnRH cDNA sequence, PCR products of the expected size were obtained from human liver, heart, skeletal muscle, kidney, placenta, and pituitary. The authenticity of the PCR products was confirmed by Southern blot analysis with an internal oligonucleotide primer as probe. Similarly, using specific oligonucleotide primers for the GnRH receptor selected from the human pituitary GnRH receptor cDNA sequence, PCR products of the expected size were amplified from human liver, heart, skeletal muscle, kidney, placenta, and pituitary, and these strongly hybridized with the human GnRH receptor cDNA on Southern blot. Cloning and nucleotide sequencing of the PCR products for the GnRH and GnRH receptor from heart revealed identical sequences when compared to the human placental GnRH and pituitary GnRH receptor cDNAs, respectively. These data demonstrate for the first time the existence of GnRH and GnRH receptor mRNAs in normal human non-reproductive tissues and suggest that GnRH and its receptor may play an important role in the regulation of cellular functions in an autocrine or paracrine manner, in addition to regulating the secretion of gonadotropins from the anterior pituitary.