An important feature of childhood acute lymphoblastic leukemia (ALL) is the risk of testicular relapse in affected males, which may occur months or years after induction of remission. However, little is known about the factors that regulate leukemic cell survival and resistance to chemotherapy in the testis. In the present study, incubating ALL cell lines and primary cells from ALL patients at 33 degrees C resulted in increased survival, resistance to chemotherapeutic agents and upregulation of bcl-2. Acute myeloid leukemia cell lines incubated at 33 degrees C also showed increased survival and resistance to chemotherapeutic agents, but did not demonstrate upregulation of bcl-2. This may be important in determining survival of ALL cells at lower temperatures in the testis.