A reagent for four-part differentiation of white blood cells is provided. In one embodiment the reagent has an osmolality below 50 mOsm/kg H2O. A method for differentiating white blood cells using the reagent is also provided. The disclosure provides for a rapid lysis of red blood cells and four-part differentiation of white blood cells. The reagent may be simple in components and a surfactant is not necessary, but optional. A wide range of pH values may be suitable for the reagent.