Of 395 male pediatric patients with previously untreated acute lymphoblastic leukemia, 20 (5%) exhibited testicular infiltration prior to or concurrent with their first bone marrow relapse. Fourteen occurred as an isolated relapse and six occurred concomitant with bone marrow and/or central nervous system relapse. Nine of the 20 relapses were in patients who had discontinued therapy after completing three years of continuous complete remission. Factors found to be independently associated with an increased risk of testicular relapse during maintained remission included pretreatment lymphadenopathy, and to a lesser extent, initial hemoglobin level and initial platelet count. Pretreatment splenomegaly and lymphadenopathy appear to imply an increased risk of testicular relapse for those patients who have their maintenance therapy discontinued. Time from testicular relapse to bone marrow relapse or death was significantly shorter for patients with testicular involvement while receiving chemotherapy when compared to patients with testicular relapse after discontinuing therapy. In those patients achieving three years of continuous complete remission, subsequent testicular relapse occurred significantly more often in patients who discontinued therapy than a similar group who continued therapy. In a group of 76 males who received presymptomatic gonadal radiation immediately after achieving an initial marrow remission, protection appears to have been provided against the manifestation of testicular leukemia during maintained remission.