Human T-cell leukemia virus type I (HTLV-I) was the first human retrovirus isolated and is responsible for at least one form of human leukemia. The pathogenic mechanism(s) whereby HTLV transforms T lymphocytes in vivo is(are) obscure due to its long-term latency and the lack of practical representative animal models. The tax gene of HTLV-I has been implicated in this transformation process because of its ability to transactivate several cellular genes associated with T-cell replication and activation. Here, transgenic mouse models are discussed that express the Tax protein of HTLV-I and provide insights into its role in the cellular transformation process.