Interferon alpha (IFN-alpha) has a documented activity against malignant melanoma with a response rate of only approximately 20%. It would therefore be of considerable importance if patients likely to respond could be identified. The degree of mononuclear cell infiltration in primary tumours has been reported to correlate with a favourable prognosis. This investigation used monoclonal antibodies, anti-CD4, -CD8 and -CD11c, to identify subsets of tumour-infiltrating mononuclear cells in fine needle aspirates to study whether the presence of such cells correlates with the therapeutic effect of IFN-alpha. Twenty-one patients with systemic and 20 with regional metastatic malignant melanoma were studied before initiation of IFN-alpha treatment. A statistically significant correlation (P < 0.001) was found between the occurrence of CD4+ lymphocytes in fine needle aspirates and the therapeutic benefit of IFN-alpha in patients with systemic disease. Ten out of 11 with moderate to high numbers of infiltrating CD4+ lymphocytes achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, nine out of ten had progressive disease. Similar results were found in patients with regional disease.