BACKGROUND: A scarcity of data exists relating to the effect of amyloidosis of Familial Mediterranean fever (FMF) on the autonomic nervous system. Our aim was to further investigate the presence of dysautonomia in FMF-AA amyloidosis, using a comparative case series design. MATERIAL AND METHODS: The study group consisted of 40 patients with FMF: 20 without co-morbidities or amyloidosis and 20 in various stages of renal amyloidosis. Time domain and power spectral analyses of heart rate dynamics were performed according to accepted procedures. Findings were compared with 20 healthy control subjects. RESULTS: No statistically significant differences were found in any of the studied heart rate variability (HRV) parameters between patients with uncomplicated FMF and controls. In contrast, patients with progressive amyloidosis (post renal transplantation or on dialysis) had significantly lower HRV parameters compared to control subjects (i.e. mean low frequency power spectral components 104.30 ms(2) vs. 172.09 ms(2), p <0.05, mean standard deviation of all normal RR intervals 32.27 ms vs. 51.51 ms, p <0.05, mean HRV triangular index 9.08 vs. 15.82, p <0.05). The adjusted odds ratio was 14.5 (95%CI 1.21-165.03, p = 0.04) for HRV triangular index lower than 12.2 in the progressive amyloidosis group, 41.24 (95%CI 1.81-938.68, p = 0.02) for low frequency power spectral components values lower than 142.35 ms(2), and 12.67 (95%CI 1.04-153.96, p = 0.04) for standard deviation of all normal RR intervals values lower than 40.15?ms. CONCLUSION: Amyloidosis of FMF, particularly at a progressive stage, is associated with HRV abnormalities suggestive of the presence of autonomic nervous system dysfunction.