Between 1976 and 1986, 2,093 children with ALL were enrolled in three consecutive generations of trials conducted by the Associazione ltaliana Ematologia Oncologia Pediatrica (AIEOP). A 50% event-free survival at 5 years was achieved overall in this population, approximately accounting for more than 50% of the entire childhood ALL population in Italy. Participation in the group protocols increased from the original seven founding centers t o the current 37 institutions. Results in the standard population (non-T irnmunophenotype, non-FAB L3, and < 50,000 white blood cells [WBCl/ml) were considerably better with more recent, more aggressive protocols. The two major results in this population (N = 540) were a rela-tively low incidence (8% at 5 years) of central nervous system (CNS) relapse in the "good"-risk population (< 70,000 WBC, ages 3-6 years, and FAB L l ) , without the use of cranial irradiation, and a projected 4-year disease-free interval for bone-marrow relapse of 80% in the "average"-risk group, where a three-drug reinduction program was adopted after consolidation. Overall, the event-free survival of the most recent generation (protocol 82, median follow-up time of 38 months) is 66% at 4 years (95% confidence limits [CL] 61-71). Based on these 10 years of experience, the general strategy of the group for the 90s is outlined and discussed.