Abstract: Decay accelerating factor (DAF) is a widely distributed glycoprotein which aids in the inactivation of complement. DAF is also a cellular receptor for certain group B coxsackieviruses (CVB) and is responsible for the viral hemagglutinating activity for human red blood cells (RBC). Healthy, young female volunteers donated blood on days 11 and 22 of the ovarian cycle. Samples were categorized into luteal and follicular phases based on serum progesterone levels (P4 either <2.0 ng/mL, follicular; P4 ≥ 2.0 ng/mL, luteal) and analyzed by flow cytometry for DAF expression on RBC and CD21+ B lymphocytes. Cycling females showed significant variation in CVB-induced hemagglutination and % RBC or CD19+ cells which were DAF+. There was a strong correlation between serum estradiol levels and % RBC expressing DAF (P < 0.01) in the follicular, but not in the luteal ovarian phase. Infection of white blood cells with green-fluorescent protein CVB (GFP-CVB) showed a correlation between infectivity of CD19+ cells and DAF expression. This indicates that women may show differential susceptibility to CVB infection in the luteal and follicular phases of the ovarian cycle.