A covalent conjugate of alpha-foetoprotein (AFP) and horseradish peroxidase (HRP) has been used to follow the internalization pathway of this serum protein in early and late passages of primary cultures of mouse embryonic fibroblasts as well as in a spontaneously immortalized cell line. AFP, as transferrin (Tf) used in parallel as a control, are endocytosed through coated pits and vesicles and move then to endosomes in every case; in cells of the late passages, at least a part of the internalized proteins would be routed to lysosomes. Cells of three different established human mammary cancer lines (MCF-7, Evsa-T, T-47D) internalize AFP-HRP through coated pits and vesicles. Such localization of the conjugate is practically never detected in normal human mammary epithelial cells in primary culture. Taken together, these results are in agreement with the view that AFP receptors are expressed at the surface of proliferating mouse embryonic fibroblasts and human mammary epithelial cancer cells but absent from the surface of normal human mature cells of the same origin.