Antiphospholipid antibodies (APA) and other coagulation abnormalities have been associated with an increased risk of venous, arterial, and placental thrombosis and recurrent pregnancy loss (RPL). Factor V Leiden (a point mutation [1691G-->A] in the factor V gene), the prothrombin 20210G-->A mutation, and homozygosity for a common polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene (677C-->T) have been associated with arterial and venous thrombosis and arterial occlusive disease. We explored an association between these markers of thrombophilic states and RPL.Prospective case-control evaluation.University-associated private practice.Fifty nonpregnant women with three or more pregnancy losses and 50 healthy, nonpregnant controls.None.Anticardiolipin and antiphosphatidylserine antibodies were detected in serum by ELISA. Polymerase chain reaction was performed to identify the factor V Leiden (1691G-->A) mutation, the thermobile MTHFR (677C-->T) mutation, and the prothrombin 20210G-->A mutation.The following were identified by restriction fragment-linked polymorphism analyses: 1 (2%) factor V Leiden heterozygosity; 1 (2%) prothrombin 20210G-->A heterozygosity; and 4 (8%) thermolabile MTHFR homozygosity. None of these mutation frequencies in women with RPL were statistically significantly different from controls.These data suggest that factor V Leiden, thermolabile MTHFR (677C-->T), and prothrombin 20210G-->A are not found at an increased frequency in women with a history of early RPL.