Five antibodies that stained renin in the kidney were used to investigate the presence of renin in human placenta and fetal membranes. Despite a large number of experimental approaches to enhance penetration of the immunoglobulins, only two of them showed immunostaining in placenta and fetal membranes. Staining was found in placental syncytiotrophoblast, the amnionic epithelium overlying the placenta, and in glandular epithelial cells present in the decidua adhering to the fetal membranes. It was most consistent, however, in a small infiltrating cell type dispersed through the fetoplacental layers. The two antibodies that revealed immunostaining in all preparations showed high affinity cross-reactivity with cathepsin D. Among other, less plausible, explanations, this raises the possibility that the bulk of 'renin' found in placenta and fetal membranes is not identical to renal renin, but may be cathepsin D or a substance related to both cathepsin D and renin.