Studies were made to test immune reactivity between anti-leukemic cell sera and nonadherent peripheral blood cells from patients with leukemic and nonleukemic P. vera. Cells from seven patients with leukemic P. vera had complement-dependent cytotoxicity test results showing more than 80% cell killing. In comparison, leukocytes from 37 nonleukemic and nonpolycythemic subjects, with and without blood disorders, failed to show significant cytotoxicity. Cells from 20 patients with nonleukemic P. vera and 10 patients with myelofibrosis, thrombocythemia, and "spent" P. vera also failed to react. Three nonleukemic P. vera patients showed a positive reaction that became progressively stronger; they developed leukemia at a later date. The association of positive reactivity before leukemia is overt, to later development of acute leukemia calls attention to the possible use of immunologic technology as a means of early diagnosis of leukemia.