An evaluation of general immunologic reactivity was performed in 116 patients with malignant melanoma and in 40 patients with skeletal and soft tissue sarcoma who received adjunctive immunotherapy. An excellent correlation was observed between delayed cutaneous hypersensitivity to DNCB and the clinical extent of malignancy. Eighty percent of patients with Stage I disease were DNCB positive, whereas only 37% of Stage III patients were reactive on initial testing. A method for sequential evaluation of DNCB response was established, and revealed that variations in immune reactivity occurred that also correlated with the patient's clinical course. Persistence of nonreactivity to DNCB or conversion from a reactive to an anergic status was associated with postoperative recurrence in more than 80% of the patients. Conversely, conversion from an anergic to a reactive status was observed if tumor control was achieved. These results indicate that the defect in systemic immunity is closely associated with tumor cell burden, and that sequential evaluation of DNCB reactivity is a clinically useful monitor of disease progression.