One hundred eighty-two patients undergoing initial surgical therapy for primary malignant melanoma were evaluated for delayed hypersensitivity using a battery of recall antigens prior to surgery. Fifty-six patients were also sensitized with 2, 4-dinitrochlorobenzene. All tumors were classified by Clark-Mihm levels and the patients were clinically staged. They were followed up for an average period of 55 months. There was no significant difference in the ability of patients with varied Clark-Mihm level lesions to mount a delayed hypersensitivity response to the recall battery or to 2, 4-dinitrochlorobenzene. Thirteen stage I melanoma patients in whom recurrence developed at a distant site exhibited no difference in immune responsiveness when compared to 148 patients in whom recurrence did not develop when both groups were tested with recall antigens. No difference was noted in patients with stage II disease in whom recurrence developed, as measured by reaction to these same antigens. Twelve patients demonstrated anergy to recall antigens, in none of whom has recurrence developed to date. Fifty-six patients who were tested with 2, 4-dinitrochlorobenzene showed no difference in reactivity with tumors classified at any of the Clark-Mihm levels. Anergy demonstrated by delayed hypersensitivity skin testing appears to reflect increasing tumor burden, rather than a preexisting deficiency that can be used to predict patients at high risk for the development of recurrent disease.