Important CO2 unloading occurs during hemodialysis (HD) when acetate-buffered dialysate is used. This is accompanied by alveolar hypoventilation. To gain more insight into the mechanisms of this alveolar hypoventilation, breathing patterns were studied in 5 patients with end-stage renal failure during HD using acetate-buffered dialysate, which induces CO2 unloading, or bicarbonate without CO2 loss. Ventilation was continuously measured with calibrated respiratory inductance plethysmography using techniques of multiple linear regression analysis. At regular intervals, arterial blood gas was sampled and expired air was analyzed. Breathing patterns were analyzed for VE, VT, TI, TE, and VT/TI. All data were compared with the respective starting value and with the respective value in the other setup. A greater decrease in ventilation was seen during HD with an acetate-containing dialysate because of irregular breathing patterns that resulted in a prolongation of expiratory time. Important variations in tidal volumes, striking apnea periods, and occasional periodic breathing were observed. We suggest that these irregularities are due to CO2 unloading leading to the point where ventilation is totally mediated through the output of the peripheral chemoreceptors.