ABSTRACT Receptors for insulin-like growth factor II (IGF-II) have been identified in many tissue types and have been shown to differ widely in their specificities and affinities. We have characterized the IGF-II receptor in rat liver microsomal membranes, both in the intact membrane and in a solubilized extract. Binding was time- and temperature-dependent and was unaffected by changes in pH in the range 6–9. Half-maximal displacement was obtained with 0·33 ng IGF-II/ml standard, and Scatchard analysis showed a class of receptors with an affinity for IGF-II of 1·33 ± 0·36 × 10¹⁰ litres/mol which increased threefold in the presence of Ca (1 mmol/l) to 3·74 ± 0·89 × 10¹⁰ litres/mol. There was also a threefold decrease in the rate of dissociation in the presence of Ca. Cross-reactivity with IGF-I was < 1% and there was no cross-reactivity with insulin. Infusion of rat GH or prolactin for 1 week, at the rate of 175–200 μg/day, into female rats had no effect on IGF-II binding in control animals, but rat GH infusion caused a 60% increase (P< 0·001) in binding in hypophysectomized rats by increasing the number of receptors. These studies demonstrate that rat liver microsomal membranes contain a highly specific, high-affinity receptor for IGF-II which may be under partial GH control J. Endocr. (1987) 113, 27–35