Among 131 boys with advanced (stage III or IV) non-Hodgkin's lymphoma (NHL) consecutively treated at St. Jude Children's Research Hospital, testicular involvement was present at the time of diagnosis in six and as an isolated site of relapse in three. Testicular involvement was not seen in any patient with localized (stage I or II) disease. Four of the six patients with involvement at presentation are free of disease 2.9+ to 8.3+ years after diagnosis, following chemotherapy alone (three patients) or chemotherapy plus orchiectomy. Overt testicular relapse while on therapy resulted in death from progressive disease in two patients; the third relapsed after completing therapy for Burkitt's lymphoma and is in second remission after chemotherapy, orchiectomy, and scrotal irradiation. The prolonged remissions seen in children with testicular involvement at diagnosis suggest that scrotal irradiation may not be necessary in chemosensitive disease. By contrast, testicular relapse on therapy appears to indicate drug-resistant disease and a poor prognosis, despite testicular irradiation and chemotherapy.