The clinical correlations of serum tumor necrosis factor alpha (TNF-alpha), a cytokine which can be released from leukemic blasts, has not been extensively studied. We have analyzed serum TNF-alpha in 20 ANLL, one CML-myeloblastic crisis, and 14 ALL adult patients by using a commercial ELISA kit. Sterile serum samples were taken on day 0, day 7, during remission and relapse with a mean follow-up period of 4.2 (1-19) months. After a median of 7 days following chemotherapy, serum TNF-alpha decreased both in responding ANLL (p = 0.004) and ALL (p > 0.05) but remained high in refractory leukemias. Values on day 7 were significantly different between responding and refractory patients in both ANLL (p = 0.0027) and ALL (p = 0.0099). At relapse, serum TNF-alpha increased starting at a median of 3 months preceding clinical symptoms in ANLL (p = 0.002). However, the relapse of ALL coincided with a slight increase which was not significant (p > 0.05). Together these findings indicate that serum TNF-alpha can be used as an early predictor of clinical response and relapse in ANLL.