In order to assess the prognostic value of nephromegaly (kidney enlargement ≥ 2 SD from mean for age) in children at diagnosis of acute lymphoblastic leukemia (ALL), kidney size was investigated by intravenous pyelogram (IP), according to the method of Eklöf and Ringertz, in 101 children diagnosed with ALL in the period of 1975-1983. In the same period 103 additional patients with ALL were not investigated with IP for logistical reasons. Characteristics at the diagnosis of ALL in the patients of the investigated and non-investigated (with IP) groups were quite similar and event-free-survival (EFS) curves superimposable. Eighty-nine (50 males and 39 females, median age 61 months) out of 101 patients underwent IP before starting any therapy and were evaluated in the study; 27 (30.3%) presented with nephromegaly (bilateral in 13 cases and unilateral in 14). With a median follow-up time of 14.4 years (range 11-19 years), the EFS at 15 years from diagnosis was 18.5% (SE 9.5) in the nephromegalic group and 48.4% (SE 6.4) in the non-nephromegalic group. The association of poorer EFS with nephromegaly was confirmed when the comparison was adjusted by white blood cell count and age at diagnosis in a Cox regression model. Nephromegaly at diagnosis of childhood ALL may have an independent prognostic value in patients treated with ‘not intensive’ protocols; however, this finding should be confirmed in patients treated uniformly with contemporary intensive protocols.