This study investigates the peripheral circulatory and autonomic response to volume withdrawal in haemodialysis based on spectral analysis of photoplethysmographic waveform variability (PPGV). Frequency spectrum analysis was performed on the baseline and pulse amplitude variabilities of the finger infrared photoplethysmographic (PPG) waveform and on heart rate variability extracted from the ECG signal collected from 18 kidney failure patients undergoing haemodialysis. Spectral powers were calculated from the low frequency (LF, 0.04-0.145 Hz) and high frequency (HF, 0.145-0.45 Hz) bands. In eight stable fluid overloaded patients (fluid removal of >2 L) not on alpha blockers, progressive reduction in relative blood volume during haemodialysis resulted in significant increase in LF and HF powers of PPG baseline and amplitude variability (P < 0.01), when expressed in mean-scaled units. The augmentation of LF powers in PPGV during haemodialysis may indicate the recovery and possibly further enhancement of peripheral sympathetic vascular modulation subsequent to volume unloading, whilst the increase in respiratory HF power in PPGV is most likely a sign of preload reduction. Spectral analysis of finger PPGV may provide valuable information on the autonomic vascular response to blood volume reduction in haemodialysis, and can be potentially utilized as a non-invasive tool for assessing peripheral circulatory control during routine dialysis procedure.