Killing of autologous melanoma (auto-Me) was obtained with pooled allostimulated peripheral blood lymphocytes (PBL) in 34/42 cases and found not to be due to a cross-reactivity between melanoma and allogeneic normal antigens. To see whether generation of tumour cytotoxic PBL by allostimulation was due to release of IL-2, PBL from 34 patients were divided into two aliquots and stimulated either by alloantigens or IL-2. Allostimulated PBL were cytotoxic for auto-Me in 30/34 cases (85%) whereas IL-2 generated tumour cytotoxic cells in 22/34 cases (64%). Lysis of K562, a target for monitoring NK-like activity, was obtained in 95-100% of cases with both stimuli. A similar frequency of OKT3+, OKT4+, OKT8+ and HNK1+ cells was found in PBL activated by allostimulation and IL-2, whereas a higher frequency of OKM1+ cells was evident in IL-2-stimulated PBL. Cold-target competition studies indicated that allostimulation generated at least two different types of effectors, one lytic to auto-Me but not to K562, and the other which lysed both targets. Allostimulated, FACS-separated T3- cells killed both auto-Me and K562 cells whereas T3+ cells lysed only auto-Me. It is concluded that allostimulation generated two subpopulations of auto-Me killer cells, one of the T lineage and the other NK-like, which both can destroy auto-Me targets.