A hemodialysis machine (10) is disclosed comprising: a blood circuit (184, 186); a dialysate circuit (220); and a dialyzer (36) placed in communication with the blood circuit and the dialysate circuit. The hemodialysis machine is operable to perform a priming sequence in which dialysate is used to prime a first portion of the dialysate circuit and a physiologically compatible solution, other than dialysate, is used to prime a second portion of the dialysate circuit, the dialyzer and the blood circuit.