Twenty-five patients with malignant melanoma were studied to determine the mechanisms underlying decreased cellular immunity in this disease. Sixteen patients were examined following surgical resections of tumor, and nine patients had evidence of metastases. Patients with metastatic disease (group II) had decreased lymphocyte transformation to concanavalin A (48,255 +_ 30,074) compared with controls (83,550 + 41,277) and patients free of disease (group I) 110,231 +_ 59,990) (P > 0.01). Rigorous depletion of monocytes by adherent techniques resulted in an improvement in blastogenesis in seven of nine group H patients, whereas controls and group I patients had marked decreases in reactivity. Indomethacin also improved lymphocyte reactivity; a mean of 166.4% was recorded in five metastatic disease patients studied, as against a mean of 2% in group I and 9.65% in controls. In seven patients followed serially the presence of adherent suppressor cells tended to correlate with progressive disease, shorter survival, and decreased skin test reactivity.