The NM23 genes, encoding for the red blood cell nucleoside diphosphate kinases A and B, have been found to serve as metastasis-suppressor genes in experimental animal models of tumour progression, and in some, but not all cancers in man. To investigate the role of NM23 in the progression of human malignant melanoma, we studied the expression and distribution of the nm23 protein with a sensitive immunohistochemical technique and a well-characterized monoclonal antibody in 41 benign pigment cell lesions and 71 uniformly treated malignant melanomas with a long follow up-up. In benign naevi, the junctional nests frequently expressed nm23 protein, whereas the immunoreactivity tended to decrease when the lesions matured. All malignant melanomas expressed nm23 protein in their vertical and/or radial growth phases, and the immunoreactivity tended to increase towards the deeper parts of the lesion. No relation was found between nm23 expression and patient outcome. In addition, nm23 was found in activated lymphoid cells, and this feature was significantly associated with a brisk lymphocytic stroma response in malignant melanomas. Our data are at variance with previous mRNA studies on malignant melanoma, and indicate that routine immunohistochemical analysis for nm23 protein on paraffin-embedded tumour tissue cannot reliably be used as a prognostic marker for patients suffering from malignant melanoma. In contrast, our findings suggest that the nm23 protein in pigment cell lesions is related to the proliferative or activated state of pigment cells, rather than to their metastatic potential.