The effect of glucocorticosteroids upon the poly(A) synthetic and degrading activity has been studied in steroid sensitive and resistant human leukemic cell lines. At least a two-fold increase in the levels of poly(A) polymerase activity was found in soluble, cytoplasmic extracts from the steroid sensitive human malignant T-cells of the MOLT3 line after 24-h treatment with dexamethasone. Longer exposure time of the cultured cells to the steroid resulted in a gradual decrease of the poly(A) polymerase activity level. Pretreatment of the cells with progesterone, a competitive inhibitor of dexamethasone, prevented the dexamethasone induced increase in the level of poly(A) polymerase activity, while progesterone alone had no effect on the enzyme level. In contrast, the levels of poly(A) nucleases activity remained constant following steroid treatment. In the steroid resistant human leukemic B-cell line Daudi no alterations in the poly(A) metabolizing enzymes could be measured in response to dexamethasone. Thus we suggest that poly(A) polymerase levels may be used to predict sensitivity of leukemic cells to glucocorticosteroid treatment.