Peptide 23, the rat homolog of the human pancreatitis-associated protein (PAP)/hepatocarcinoma-intestine-pancreas (HIP) protein, has been identified in primary culture of rat pituitary cells. Its secretion was shown to be stimulated by GH-releasing factor and inhibited by somatostatin in a similar fashion to GH. This observation led the researchers to speculate that peptide 23 does have a physiological hormonal role. We tested this hypothesis by screening by RT-PCR reactions the expression of the PAP/HIP gene in several human pituitary adenomas, especially GH-producing adenomas. Our results show a weak expression of the PAP/HIP gene in the pituitary gland and in most of the tumors, but independent of their origin. The significant homology of the PAP/HIP gene to the Reg gene family prompted us to study in the same pituitary adenomas the presence of the related Reg genes. Reg expression was never observed in the adenomas tested or in the pituitary gland. In contrast, the RegL transcript was observed in pituitary gland and in some subtypes of adenomas. We then extended our work to normal adults and developing human tissues to compare the expression patterns of the PAP/Reg gene family. We observed the presence of the PAP/HIP transcript in each tissue tested. In contrast, the Reg gene was expressed only in fetal pancreas and in some adult tissues, whereas the RegL gene was expressed not only in fetal pancreas but also in fetal colon and brain as well as some adult tissues. In conclusion, our results show that all of the human fetal and adult tissues examined express at least one of the different transcripts of the PAP/Reg family, suggesting that the regulation of these homologous genes is coordinately controlled.