Two variant sublines of the murine 3LL carcinoma with divergent potentials for lymphatic metastasis were used to assess the relationship between tumor cell potential for lymphatic metastasis and its ability to adhere specifically to lymphatic tissue. Using fresh cryostat sections of lymph nodes and spleens, it was found that tumor cell adhesion to the lymphatic tissue but not to control sections of the brain correlated well with their ability to metastasize lymphatically. On the other hand, there was no correlation between tumor cell attachment to isolated lymphocytes in vitro and their potential for lymphatic metastasis. When tumor cells were pretreated enzymatically or with the metabolic inhibitor tunicamycin with the aim of modulating cell surface carbohydrates, adhesion to the lymph node sections could be significantly reduced, implicating cell surface glycoproteins and in particular galactosyl groups in the binding. The results suggest that tumor cell attachment to lymph node cryostat sections could provide a useful tool in the study of host-tumor interactions in lymphatic metastasis.