Inasmuch as several cooperative research groups currently require routine testicular biopsy in boys with acute lymphocytic leukemia before cessation of therapy, we performed bilateral open wedge biopsies in 38 boys aged 4 1/2 to 18 years, all of whom were completing 3 years of therapy, were apparently in complete remission, and had palpably normal testes. Biopsy specimens from two other patients were examined during therapy for specific clinical indications. Among the 40 patients, one biopsy revealed leukemia bilaterally; 39 patients had negative biopsy results, three of whom had overt, biopsy-proved testicular relapse 6 weeks to 17 months after normal biopsy. All four patients with testicular relapse are in complete remission six to 50 months after testicular irradiation. We conclude that random sampling during routine testicular biopsies may fail to demonstrate occult leukemia. and that the high rate of complete remissions following retrieval therapy after overt testicular relapse makes routine biopsies before cessation of therapy unnecessary.