Since September 1979, 44 stage III melanoma patients treated with intralymphatic immunotherapy (ILI) with an oncofetal antigen (OFA-I)--enriched tumor cell vaccine (TCV) had evaluable humoral immune responses and clinical follow-up. Fourteen patients (32%) had stabilization or regression of tumors or remained free of resected disease. The median survival was 17 months, compared with 6 months for controls (P less than 0.001). Humoral immune responses were monitored by immune adherence using an OFA-positive human melanoma cell line, M14, as target. Alloantibodies were removed by absorption with L14 lymphoblasts autologous to M14. Twenty-two patients (50%) developed elevated antibody titers within 4 months, and 12 of the 22 (55%) had no disease progression. In contrast, 20 of 22 patients (91%) who failed to develop elevated titers had disease progression (P less than 0.01). The median titer was significantly higher during the first 4 months in the group whose disease did not progress (P less than 0.04). This study demonstrated that ILI with allogeneic OFA-I-enriched TCV can induce objective tumor regression and prolonged survival in patients with disseminated melanoma. Furthermore, because the specific humoral immune response correlates with clinical results, immunization efficacy can be monitored within a short period of time, which should aid future efforts to achieve optimal immunotherapy.