Oncogenic retroviruses can cause cancer in various species, including cats, birds and rodents. They are generally divided into two categories, which display distinct pathogenic features. The acute-transforming retroviruses induce polyclonal tumors within 2 to 3 weeks after infection of the host, and are capable of transforming cells in tissue culture. In contrast, the slow-transforming retroviruses cause mono-or oligoclonal tumors after a latency period of several months, and are usually unable to transform cells in vitro [38,350,375]. These differences in pathogenic properties reflect two distinct molecular mechanisms of retroviral oncogenesis. Acute-transforming retroviruses have replaced viral genes with a transduced cellular gene, or part of a gene, that is responsible for the oncogenic activity. Slow-transforming retroviruses do not carry viral oncogenes, and their capacity to induce neoplasms is based on the ability of the retroviral DNA-intermediate, the provirus, to integrate in the host DNA, and mutate or transcriptionally activate flanking cellular sequences. These and other relevant aspects of slow-transforming retroviruses will be summarized in Section 2. If the mutations caused by proviral insertions confer a selective growth advantage, the affected cell will expand in a clonal fashion. Because of this causal relation between proviral insertion site and tumorigenesis, retroviral integration patterns in tumors that are induced by slow-transforming retroviruses appear clonal or oligoclonal, whereas infected normal tissues reveal a seemingly random distribution of proviruses in their DNA [78,342]. In 1981, Hayward et al. showed that slow-transforming retroviruses can be used both as insertional mutagens and as molecular tags [142], and since then a large number of genes implicated in oncogenesis have been identified by'provirus tagging', involving molecular cloning of host cell DNA adjacent to integrated proviruses, either by conventional techniques [127] or by PCR amplification [339]. While many of the initial studies were focused on avian leukosis-sarcoma virus (ALV) induced lymphoid leukosis [74, 75], this approach has been most successfully used in various murine tumor systems. A large series of common insertion sites has been found for leukemia viruses in diseases of the hematopoietic system, and for mouse mammary tumor virus (MMTV) in mammary carcinomas. Hence, the emphasis of this review will be on these two retrovirally induced diseases. In the last sections we will discuss the use of retroviral insertional mutagenesis in a variety of mouse model systems or in vitro systems. Oncogene-bearing transgenic mice and mice with targeted disruptions in oncogenes or tumor suppressor genes, as well as a number of applications in cultured cells have significantly increased the potential of proviral tagging, and it can be expected that this trend continues with the development of novel detection techniques and improved viruses or transposon systems.