We have analyzed the clinical significance of the plasma level of tumor necrosis-alpha (TNF-alpha) detection in childhood acute lymphoblastic leukemia (ALL) at diagnosis. 49 patients (pts) with B-lineage ALL (3-17 years of age) and 30 healthy children (age-related control) were enrolled in study. The mean value of the level of TNF-alpha was 43.4 +/- 8.1 pg/ml in ALL pts and 30.7 +/- 3 pg/ml in control. In ALL pts the level of TNF-alpha positively correlated with blast cell count in peripheral blood (R = +0.432; P = 0.008); negatively correlated with percentages of S-phase leukemic cells (R = -0.446; P = 0.042) and culture-induced apoptotic cells (R = -0.411; P = 0.057). Pts with TNF-alpha level above the median value were characterized by higher WBC count (P = 0.025), lower percentage of S-phase leukemic cells (P = 0.02) and tendency to lower percentage of apoptotic cells (P = 0.07) vs pts with TNF-alpha level below the median value. No significant association of the level of TNF-alpha with treatment response at days 8 and 15 or 3-year overall survival was defined. We conclude that the elevated plasma level of TNF-alpha is a useful marker to assess disease activity/progression, but not prognosis of childhood B-lineage ALL.