Forty patients with various types of myeloproliferative disorders were evaluated immunologically. Serum immunoglobulin levels were within the normal range in most patients and no monoclonal gammopathies were detected. Serum C'3 levels were decreased in 19 of 40 (48%) patients. The response of peripheral blood lymphocytes to phytohemagglutinin was decreased in 26 of 40 (65%) and to pokeweed mitogen in 18 of 28 (64%) patients studied. Lymphocytes from patients with polycythemia vera were least affected. Unstimulated lymphocytes from some patients demonstrated markedly increased thymidine uptake activity. Despite the diminished mitogenic response, only 2 of 33 patients (6%) were anergic by intradermal skin testing. There was no association between depressed lymphocyte response and recent chemotherapy except in chronic myelogenous leukemia where 6 of 8 patients were receiving cytotoxic therapy when studied. These observations suggest that most of our patients with myeloproliferative disorders have abnormal cellular responses in vitro, but that delayed hypersensitivity and humoral responses are minimally affected.