the relationship between estrous phase and immune response in female rats was studied using two designs. in the between subjects design, groups of five rats were tested for antigen binding capacity and estrous phase on each of the ten days following secondary exposure to an hsa antigen. in the within subjects design, fourteen rats were tested for estrous phase at time of antigen exposure and for antigen binding capacity on each of the ten days following secondary exposure. estrous phase was determined from microscopic examination of vaginal smears and phases were categorized according to high or low levels of estrogen and progesterone. both designs showed a significant increase in immune response over the ten days. the within subjects design showed that higher estrogen levels at the time of antigen exposure were accompanied by elevated immune response. this finding shows that naturally occurring fluctuations in estrogen level at the time of a challenge to the immune system have an influence on the immune response.