Rh incompatibility occurs when an Rh-negative mother carries an Rh-positive fetus, creating risk for maternal isoimmunization. When fetal Rh-positive red blood cells cross the placenta, the mother's immune system produces anti-D antibodies. First exposure produces IgM (cannot cross placenta — first baby usually unaffected). Subsequent exposures trigger rapid IgG anti-D production that crosses the placenta, attacks fetal RBCs, causing hemolysis, anemia, hyperbilirubinemia, and potentially hydrops fetalis. Prevention with Rho(D) immune globulin (RhoGAM) at 28 weeks and within 72 hours postpartum has dramatically reduced this condition.