Parathyroid hormone-related peptide (PTHrP) has been detected in fetal serum and amniotic fluid. Using a combination of immunocytochemistry and molecular biology we have detected the peptide and its mRNA in a variety of fetal tissues throughout gestation. Tissue-specific mRNA isoforms were observed, the pattern of hybridization of which changed throughout gestation. In addition, the intensity and pattern of immunocytochemical localization of the peptide was found to vary over the time-period studied (8∓30 weeks). PTHrP is expressed by a variety of tumours associated with the syndrome of humoral hypercalcaemia of malignancy and probably accounts for the hypercalcaemia by virtue of its limited amino acid homology with parathyroid hormone. These data demonstrate for the first time that PTHrP, a tumour-related peptide, is expressed during normal human fetal development, and suggest the possibility that it may function to regulate fetal calcium balance and growth in utero.