An excess of cell multiplication over cell death is a crucial characteristic of preneoplastic and neoplastic cell populations. In many tumours, the rates of both cell birth and cell death are increased over those in the tissue of origin. Cell death may occur through active mechanisms: cellular suicide or active or programmed cell death, often referred to as apoptosis. The term 'apoptosis' was originally used on morphological grounds for a type of cell death characterized by condensation and fragmentation of cytoplasm and chromatin; however, other types of active cell death exist, in which cytoplasmic degradation by lysosomal, autophagic or proteasomal mechanisms may dominate, e.g. in some experimental mammary tumours and mammary tumour cell lines. Morphological and biochemical differences between the types of programmed cell death should be considered when selecting markers for identification and quantification of cell death. There is still a paucity of specific, efficient methods to assay active cell death, and unequivocal differentiation from degenerative necrosis, especially in tumours, may be difficult or impossible. Active cell death is regulated by a complex network of survival factors and death signals. Many mitogens of exogenous or endogenous origin not only stimulate cell birth but at the same time may inhibit cell death, i.e. increase survival. Endogenous factors also exist which induce active cell death; these include transforming growth factor beta1, CD95 or Fas ligand and tumour necrosis factor. Signal pathways leading to birth or death of cells appear to be interconnected to allow for the fine tuning of cell numbers in tissues. Active cell death can be triggered in two principal ways: by toxic chemicals or injury leading to damage of DNA or of other important cellular targets, and activation or inactivation of receptors by growth-regulating signal factors in the organism. Increases in cell proliferation or in cell survival induced by a chemical do not necessarily lead to cancer, but may indicate carcinogenic potential. Chemicals can affect the balance between replication and death of cells in a number of ways. Firstly, genotoxic carcinogens induce genetic damage which subsequently leads to activation of the suicide machinery, involving genes such as p53. As a result, cells with promutational lesions and mutations are eliminated, thereby providing protection from potentially initiated cells. Secondly, toxic doses of genotoxic or nongenotoxic agents induce acute or chronic injury, leading to cell death and subsequent regenerative proliferation. Thirdly, nongenotoxic carcinogens which are primary mitogens may increase the birth and/or inhibit the death of cells by direct interference with growth signalling pathways. This group of agents includes several trophic hormones; e.g. oestradiol stimulates both the replication and survival of mammary tumour cells. As demonstrated in the rat liver model, preneoplastic and neoplastic cells may be over-responsive to mitogenic or survival signals and thereby undergo selective growth. Conversely, preneoplastic clones and even malignant tumours may still depend on the survival effect of mitogens and regress upon withdrawal of the agent. This indicates that the mitogenic action of the agent is reversible and underlines the principal difference between genotoxic and nongenotoxic carcinogens. In conclusion, studies on cell proliferation and cell death are useful as adjuncts to carcinogenicity assays, and the results may facilitate the interpretation of effects. In conjunction with other biological data, this information may provide an indication of potential carcinogenicity.