A marked sensitivity of CLL lymphocytes to hydrocortisone in vitro was demonstrated in each of the 25 patients tested. The sensitivity was manifested by the eventual lysis of the affected cells. Malignant lymphocytes from 8 out of 14 ALL patients were found also to be in vitro sensitive, whereas CML cells, AML cells, normal BM cells, thymocytes, peripheral blood lymphocytes, and polymorphonuclear cells were resistant. Within a tested CLL lymphoid suspension it is proven that the hydrocortisone causes the specific lysis of the malignant cells leaving the normal lymphocytes undamaged. The cytolysis is not an immediate action, but is expressed within 7–8 hr of incubation. However, 30 min incubation with the hormone is sufficient for the cytolytic effect to occur 20 hr later. The possible mechanisms involved in the specific glucocorticoid induced cytolysis are discussed.