The purpose of this study was to test the autonomic nervous system function of patients with vitamin B-12 deficiency (megaloblastic anemia) by measuring heart rate variability (HRV). The study population consisted of 17 vitamin B-12 deficient patients and 15 age- and sex-matched normal volunteers. HRV was measured by power spectral analysis from which power of the low frequency (LF) peak (0.04-0.15 Hz), normalized units of the LF peak (LFNU), power of the high frequency (HF) peak (0.15-0.4 Hz), normalized units of the HF (HFNU), and ratio of power of LF to power of HF (LF:NF) were calculated Vitamin B-12 deficient patients had lon er LF, LFNU, HF, HFNU, and LF:HF ratio than normal volunteers (P < 0.05). Decreases in sympathetic indices (LF and LFNU) were greater than those measured in parasympathetic indices (HF and HFNU). All HRV parameters correlated positively with the level of vitamin B-12 (P < 0. 001) and negatively with the duration of disease (P < 0. 001). After vitamin B-12 replacement the HRV parameters of pa tien ts and controls became comparable (P > 0.05). Our data suggest that autonomic sympathetic and parasympathetic nervous activities are decreased in patients with vitamin B-12 deficiency, an abnormality that can be corrected by vitamin B-12 replacement therapy.