Based on 51Cr release from an allogeneic human melanoma cell (M1) cell-mediated (CMC) and antibody-dependent cellular cytotoxicity (ADCC) were determined in twenty-eight melanoma patients, thirty-one healthy controls, ten patients with other tumours and eleven chronic lymphocytic leukaemia (CLL) patients. The results were related to simultaneously performed microcytotoxicity (MC) tests, HL-A typing, plasma membrane fluorescence and B:T cell ratios in the peripheral blood. Furthermore, lymphocytes from six melanoma patients were tested in CMC and ADCC assays against autologous tumour cells. The following results were obtained. (1) A large number of healthy controls possessed lymphocytes which readily lysed M1 target cells in CMC and MC assays. (2) CMC activity of lymphocytes from melanoma patients was generally lower than that of control lymphocytes and decreased further with progression of the disease. (3) CLL lymphocytes were virtually non-toxic for M1 cells, even at high aggressor:target cell ratios. (4) ADCC assays with a heterologous rabbit-anti-M1 serum showed generally higher isotope release than CMC assays; this was particularly pronounced in the melanoma group and in the group of patients with other tumours. (5) No tumour-specific blocking factor could be detected in melanoma sera, as judged by the capacity of the sera to block CMC activity. (6) No obvious correlation was found between the results obtained in short-term CMC and long-term MC assays. (7) T lymphocytes, as determined by E-rosette formation, were significantly diminished in melanoma patients. (8) The HL-A type of lymphocytes from normal donors and melanoma patients did not appear to be related to high or low activity in CMC and MC assays. (9) Preliminary results of 51Cr release tests with autologous melanoma cells were encouraging with respect to the correlation of the results to the clinical course of the disease.