A Mr 78,000 protein (reduced), termed invasion stimulating factor (ISF), was purified from the conditioned medium of a bone metastasizing human prostatic PC-3 ML clone (M. E. Stearns and M. Stearns. Cancer Metastasis Rev., 12: 39–52, 1993). Scatchard analysis and affinity cross-linking studies revealed that the producer PC-3 ML cells expressed a receptor binding site (Mr ≈115,000). We found a Kd ≈425 pm and about 22,000 sites/cell. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiograms confirmed that the PC-3 ML cells expressed the receptor, whereas the ISF non-producing, noninvasive PC-3 clones (i.e., 3–4 × N.I. PC-3 cells) failed to express the ISF receptor. We conclude that a unique ISF autocrine loop characterizes the bone metastatic PC-3 ML cells.