This article reviews a long-standing hypothesis that metastases might be initiated through the generation of hybrids between primary tumour cells and tumour-infiltrating leucocytes such as macrophages. In this concept the hybrids become metastatic through expression of the leucocyte motility phenotype. A history of the hybrid hypothesis is presented along with recent evidence on how macrophage x tumour cell hybridization could account for some of the most defining characteristics of metastatic cells: aneuploidy, enhanced motility, aberrant glycosylation and, particularly seen in melanoma, phenotypic diversity. (C) 2000 Lippincott Williams & Wilkins.