The sequential biopsies and the careful clinical and laboratory studies in this large prospective study of PV patients offer a unique opportunity to properly evaluate the diagnostic and prognostic importance of the biopsy and to study the complications of this condition. The results of the study to date confirm and extend previous studies. Because of the long natural history of PV, the results of studies relating to leukemia, other myeloproliferative diseases, myelofibrosis, and effects of therapy are tentative at this time, even though the study is in its eleventh year. Hypercellularity of the marrow, together with hyperplasia and hypertrophy of megakaryocytes, is an almost constant finding in untreated PV. A very few cases (7 of 281) had relatively normal cellularities and normal megakaryocytic concentrations. Whether these findings were the result of sampling errors could not be determined, since only one site was biopsied. In any event, we found no unique clinical or laboratory features to distinguish these patients. At this time, the course of these patients appears to be the same as that of the other patients. Although increases in reticulin were regularly found during the spent phase of polycythemia, the relationship was not a precise one. For example, a moderate to marked increase in reticulin was found in 12 percent of the patients early in the course of the disease and was not predictive that the spent phase with myeloid metaplasia was imminent. In addition, in a given patient with serial biopsies taken over several years, some variability in reticulin was noted among the biopsies. Whether this represented variation in sampling or fluctuation in reticulin content could not be decided at this time. Using the standard criteria for examination of the marrows, we have found it impossible to predict which patients will develop leukemia, since the pretreatment and posttreatment biopsies almost up to the clinical onset cannot be separated from the remainder of the group.