Lymphocytes from normal subjects and patients with chronic lymphatic leukemia were assayed for cyclic AMP content and their response to effector stimulation, in terms of increased cellular cyclic AMP levels. Concentrations of isoprotere-nol, epinephrine, and prostaglandins E1, E2, and F2α which produced potent responses in normal lymphocytes were much less effective in increasing cyclic AMP levels of leu-kemic lymphocytes. The response to PGE2 was depressed from an 8-fold stimulation over basal, in the normal lymphocyte, to a 1.6-fold response in the leukemic lymphocyte. These data, along with those obtained previously with particulate preparations, indicate that a dysfunction in receptor-aden-ylate cyclase interaction may exist within the membrane of leukemic cells.