The clinical significance of initial DEAE chromatography of glucocorticoid binders in lymphoblastic disease was evaluated in an animal model. Domestic cats and dogs with lymphoblastic disease were treated with prednisone, 2 mg/kg/day, for 14 days, and the outcome of therapy was correlated with DEAE chromatograms of glucocorticoid binders, using 3H-triamcinolone as ligand. Six of 30 animals had a single-peak low-salt binder species, similar to that seen in a subset of human leukemia, and none of these responded. Of the 29 animals with chromatograms identical to normal tissues, 6 had a complete response and another 11 a partial response. This distribution of responders is statistically significant (p = 0.02). Thus, the leukemia-associated single-peak DEAE species appears to be associated with glucocorticoid resistance, as defined by clinical responsiveness. In contrast, the two- peak normal pattern is a necessary, but insufficient, criterion for defining responsive disease.