PIP: Through modification of an in vitro test for thrombosis formation, a Dutch research group has made three significant findings: 1) third-generation oral contraceptives (OCs) induce a resistance to the blood's natural anticoagulation system of a magnitude close to that induced by a mutation in coagulation factor V Leiden; 2) second-generation OCs show only part of the effect; and 3) in OC users heterozygous for the factor V Leiden mutation, resistance to the blood's natural anticoagulation system is as high as that among homozygotes for the mutation. These findings are consistent with epidemiologic data indicating a 6- to 9-fold increased risk of deep venous thrombosis among users of third-generation OCs compared with non-users. The presence of factor V Leiden raises this risk 30- to 50-fold. Drug regulatory agencies are urged to issue clear prescription guidelines to protect users of third-generation OCs from severe venous thrombosis.