Fetal antigen 1 was purified from second trimester human amniotic fluid by immunospecific affinity chromatography followed by reversed-phase chromatography. Fetal antigen 1 is a single chain glycoprotein with a M(r) of 32-38 kDa. The amino acid composition revealed a high content of cysteines, prolines and amino acids (aa) with acidic side-chains indicating that fetal antigen 1 is a compactly folded, strongly hydrophilic molecule. The N-terminal amino acid sequence (37 aa) revealed no homology to other known protein sequences, implying that fetal antigen 1 is a 'novel' human protein. When the aa sequence was back-translated into the appropriate degenerate sequence of nucleic acids, fetal antigen 1 could be partially aligned to a 'human adrenal-specific mRNA, pG2'. The indirect immunoperoxidase technique demonstrated fetal antigen 1 in fetal hepatocytes, glandular cells of fetal pancreas and in fetal adrenal cortex, whereas fetal medullary cells were fetal antigen 1 negative. In adult specimens fetal antigen 1 was exclusively found within the beta cells of the islets of Langerhans and in the adrenals with pronounced staining in the cortex. Our observations suggest that fetal antigen 1 is encoded by the mRNA defined by the cDNA clone pG2, but definitive sequencing and expression studies of this mRNA have not been achieved.