Chromosome studies in 104 patients with polycythemia vera. Chromosome studies were done in 104 patients with various stages of polycythemia vera (PV): 10 had leukemia-myelodysplastic syndrome, 28 had post-PV with myeloid metaplasia (PPVMM), 12 had PV with myelofibrosis, and 54 had PV. Chromosome studies were successful in 86 patients, 37 (43%) of whom had a chromosome abnormality. At diagnosis, 4 of 28 patients (14%) had an abnormal clone; the incidence was 78% in PPVMM and 100% in leukemia-myelodysplastic syndrome. Among the 63 patients with successful chromosome studies during the first 10 years of disease, 27% had an abnormal clone. In contrast, of the 23 patients who had the disease for more than 10 years, 87% had an abnormal clone. Chromosome abnormalities were found in 11 of the 60 patients who either were untreated or underwent only phlebotomy and in 26 of the 44 patients who were treated with myelosuppressive agents. Trisomy 8, +9, and 20q- were found in some patients early during the course of their disease and also among untreated patients. These chromosome abnormalities seem to be related to the natural course of PV rather than to therapy. Patients with a chromosomally abnormal clone at the time of diagnosis of PV had a poorer survival than did those with only normal metaphases. Cytogenetic results did not predict evolution of the disease, but they did provide clues to hematologic phenotype, duration of the disease, and consequences of myelosuppressive therapy. 