In order to study the effect of high‐dose therapy with peripheral blood stem cell transplantation (PBSCT) on the haemopoietic reserve in man, the number and composition of bone marrow (BM) and peripheral blood (PB)‐derived progenitor cells were examined in 137 cancer patients. In 45 patients, paired samples from BM and PB were obtained before PBSC mobilization and 6–27 months after transplantation. Following PBSCT, the proportion of CD34+ cells was significantly smaller than before mobilization (BM 1.99±0.24 versus 0.8±0.09, P+/DR− and CD34+/Thy‐1+ cells. The impairment of hematopoiesis was also reflected by a significant reduction in the plating efficiency of BM and PB samples. No relationship was found between the decrease in the proportion of CD34+ cells and any particular patient characteristics, kind of high‐dose therapy or the CD34+ cell content in the autograft. In conclusion, high‐dose therapy with PBSC transplantation is associated with a long‐term impairment of the haemopoietic system. The reduction in the number of haemopoietic progenitor cells is not associated with a functional deficit, as peripheral blood counts post‐transplantation were normal in the majority of patients.