This study examined the effect of progesterone (P4) supplementation from Days 16 to 18 post-AI on interferon-stimulated gene (ISG) expression on Day 19 in high-producing dairy cows. Gene expression levels were measured in peripheral blood mononuclear cells. Possible relationships between ISG expression and the incidence of pregnancy failure were also investigated. Cows were alternately assigned on Day 16 post-AI to a control (C: