Serial samples of peripheral blood were obtained from 75 children with acute lymphoblastic leukemia in remission. An immunofluorescence assay was used to quantitate TdT-containing (terminal deoxynucleotidyl transferase-containing) cells in the mononuclear leukocyte fraction of these specimens. Nine relapses in 8 patients were preceded by elevations (0.12-0.70%) in peripheral blood terminal deoxynucleotidyl transferase-containing cells noted 1-33 weeks prior to relapse. No such elevations were observed prior to 6 relapses in 4 patients. Peripheral blood terminal transferase deoxynucleotidyl-containing cells were elevated (0.12-0.61%) in 22 children who did not relapse over a 5-82 week period of observation. The sensitivity (67%) and specificity (68%) of this assay are inadequate to establish which patients have minimal residual leukemia.