The binding sites for mouse placental lactogen-II (mPL-II) in virgin and pregnant mouse hepatic membranes were analyzed by Scatchard analysis and affinity cross-linking. Competitive binding studies showed that mPL-II and mouse PRL (mPRL) bound to the same receptors in all liver membrane preparations, although the affinity of mPRL binding was lower than that of mPL-II binding. Two classes of receptors for mPL-II, high and low affinity, were found by Scatchard analysis. The concentration of both types of sites in liver membranes increased during pregnancy. In contrast, the affinity of both sites for mPL-II was highest in virgin female mice and declined during pregnancy. Cross-linking of [125I]iodo-mPL-II to maternal liver membranes resulted in the specific labeling of one major protein species of 67,000 daltons as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Under nonreducing conditions, two bands of approximately 63,000 and 60,000 daltons were apparent. Subtraction of the mol wt of mPL-II (22,000, reduced; 20,000, nonreduced) from the mol wt of the cross-linked complex indicated that the mol wt of the receptor was 45,000 under reducing conditions and 43,000 and 40,000 under nonreducing conditions. These observations suggest that mPL-II receptors may be present in mouse liver membranes in at least two forms.