Embryonic chicken liver adhesion molecule (LAM) has been purified to apparent homogeneity. LAM is an intrinsic membrane glycoprotein with a molecular weight of 68,000. Heteroantiserum has been prepared against LAM which blocks embryonic chicken liver cell-cell aggregation in an organ-\and species-specific fashion. This antiserum also prevents side-to-side alignment of chicken liver cells in tissue culture. The heteropolyspecific anti-LAM serum has been used in developing both qualitative and quantitative assays for LAM or LAM-related antigens. Surveys using indirect immunofluorescence have shown that LAM is present at the external periphery of liver hepatocytes and other non-parenchymal elements of both embryonic and adult liver. Reactivity is found in other epithelial tissues. This is being studied in light of the apparent tissue specificity (using in vitro assays) of the antiserum. We are attempting to isolate, stabilize and characterize monoclonal antibodies directed against embryonic chicken LAM. We have isolated many clones secreting such antibody, as measured by solid-phase radioimmunoassays and by the inhibition of embryonic chicken liver cell reaggregation. However, we have not stabilized these clones. The anti-LAM activity may be lethal for the secreting hybridoma cells. We are attempting to find growth conditions which prevent the autolysis seen in these cultures. This phenomenon seems to be unique to embryonic chickens, since we have isolated and stabilized hybridomas directed against embryonic rat LAM. We have isolated and stabilized a hybridoma that secretes a monoclonal antibody that blocks embryonic rat liver cell-cell adhesion. This hybridoma has been cloned and grown as an ascites tumor to obtain large amounts of MCA. We are characterizing the MCA antigen (i.e., molecular size, subcellular location, tissue specificity, etc.) We are currently examining mouse lymphosarcoma (RAW 117) metastatic variants selected for enhanced liver colonization by sequential in vivo selection. A correlation between cell surface LAM and liver colonization potential has been found, with heteropolyspecific antirodent LAM antiserum. The in vivo liver colonization by the tumor is also blocked by pretreatment with F(ab)1/2 fragments of immune serum. These results suggest that LAM or a related cell surface antigen may be involved in the liver specificity of this metastatic model tumor system. This hypothesis is being actively pursued.