Using a microassay for cellular immunity, tumour specific cytotoxicity was detected in 2/5 cases of ocular melanoma and 1/3 cases of primary cutaneous melanoma before treatment. Reactivity was measured against allogeneic skin melanoma target cells in short or long term in vitro culture. Lymphoid cells from patients with disseminated cutaneous melanoma were either non-reactive (4/8 cases) or gave a nonspecific cytotoxicity on target cells of diverse histogenic origins. Among tumour-free patients tested after surgery, 0/2 patients with ocular tumour were non-reactive 3-4 months post surgery. After sugical excision of cutaneous melanoma 2/2 patients gave tumour specific reactions during the first month after surgery. After longer time intervals, from 5 months to 3 years, only 1/8 patients were reactive. Preoperative radiotherapy in a total skin dose of 10,000 rad produ-ed a transient tumour specific reaction 24 h after therapy in a single case. Following local tumour excision in patients given preoperative irradiation, 2 cases which had previously demonstrated tumour specific CMI lost reactivity. Among 14 tumour-free individuals tested only after preoperative radiotherapy and surgery, at intervals from 5 day to 13 years, a single case gave tumour specific CMI. Palliative irradiation in doses 4000-4960 rad to the inguinal or axillary lymph nodes was found to induce a generalized lymphopenia within 48 h after treatment. Lymphoid cell preparations from patients with localized melanoma contained significantly increased numbers of immature cells (lymphoblasts and myeloblasts) and myeloid precursor elements. Those prepared from patients with disseminated disease had in addition elevated levels of eosinophils but reduced numbers of recoverable lymphocytes.