We previously demonstrated that the cells of lymph nodes near to a melanoma respond well to stimulation by mitogens, alloantigens, and interleukin 2 than do nodes further away. In this study we examined suppressor T-cell activity in nodes at different distances from primary melanoma, using a concanavalin A (Con A) suppressor cell assay. Tumor-free regional nodes were classified as proximal, intermediate, and distal relative to primary melanoma. Lymph node lymphocytes (LNL) were stimulated with 50 micrograms/ml Con A for 48-72 h, inactivated, and then mixed with autologous peripheral blood lymphocytes. The peripheral blood lymphocyte-LNL mixtures were stimulated with phytohemagglutinin for 3 days. Proliferation was measured by [3H]thymidine uptake during the final 18 h of culture. In 13 patients, Con A-treated LNL from nodes near to tumor were more suppressive of the peripheral blood lymphocyte response to phytohemagglutinin than those from nodes located further from tumor. T-lymphocyte subset assessment before and after Con A treatment of LNL showed no significant changes in T4:T8 ratios. Con A-induced suppressor cells could be maintained in culture in the presence of recombinant interleukin 2 and retained their suppressive activity. LNL not exposed to Con A and maintained in culture with interleukin 2 did not show suppressor cell activity. Suppressor cell activity thus contributes to the weak immune reactivity of lymph nodes near to melanoma.