Since 1975, nine children with testicular leukemia were treated at the University of Kansas Medical Center on a standard protocol. Six patients presented with overt testicular leukemia and three patients had microscopic testicular leukemia detected on a biopsy done after 3 years of continuous complete remission. All patients had an M1 bone marrow at the time of testicular relapse and one patient had a concomitant central nervous system (CNS) relapse. Therapy consisted of testicular irradiation, CNS chemoprophylaxis, and systemic reinduction chemotherapy. Systemic maintenance therapy after the testicular relapse consisted of 6-mercaptopurine and methotrexate with vincristine/prednisone pulses administered in the same basic dose and schedule as the patient's original maintenance regimen. These nine patients had a mean duration of first remission of 33 months and a mean duration of second remission of 45+ months. Four patients have relapsed (two bone marrow, one CNS, one CNS + bone marrow), but five patients remain in their second complete remission for 33+ to 94+ months from the time of testicular relapse. These results demonstrate that, in some children, testicular leukemia represents a site of temporary drug resistance and long-term second remissions can be obtained (once local disease is controlled) by using the initial maintenance chemotherapy regimen.