The nestin + perivascular bone marrow (BM) stem cell niche (N + SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N + SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n = 8), the number of N + SCN per mm 2 in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2 ± 0.78 versus 2.6 ± 0.93, P = 0.04). In the validation cohort (n = 40), the number of N + SCN was reduced (1.9 ± 0.99 versus 2.6 ± 0.90 N + SCN/mm 2 , P = 0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N + SCN/mm 2 . Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾ grade 2) and 13/20 with any type of GvHD had decreased N + SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P = 0.007) and 6/20 patients without any type of GvHD (P = 0.028). In patients tracked over time, N + SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N + SCN in aGvHD.