Adenylate cyclase (AC) and guanylate cyclase (GC) activities were studied in normal B-enriched and T-enriched lymphocytes, in lymphocytes of children with acute lymphocytic leukemia (ALL), and in lymphocytes of adults with chronic lymphocytic leukemia (CLL). AC activity was greater in normal B than T lymphocytes (215 pmole/min/mg protein versus 80 pmole in the membrane-enriched fraction) and i both increased greatly after stimulation with isoproterenol and more so with prostaglandins E and F2 alpha. In leukemic lymphocytes, AC showed depressed activity (20 pmole in ALL cells and 55 pmole in CLL cells) and was less sensitive to hormonal stimulation: this loss of sensitivity occurred to a greater extent in ALL than in CLL lymphocytes. GC activity was greater in normal T than B cells (in membrane-enriched fraction: 10.2 pmole versus 5.3 pmole). It increased little with isoproterenol and prostaglandins stimulation, and much more with sodium azide and dehydroascorbic acid stimulation. GC activity was increased in both types of leukemic lymphocytes (23 pmole for ALL cells and 18 pmole for CLL cells) and was insensitive to stimulation. Possible derangement of cyclase and cyclic nucleotide regulation in leukemic cells is suggested.