Genetic abnormalities in hemostatic proteins associated with hypercoagulability are an important hereditary risk factor for venous thrombosis. Several genetic mutations that cause hereditary disorders predisposing to thrombosis have been described, point mutation in the coagulation factor V gene (FV:R506Q), called factor V Leiden, being the most common of them. A new inexpensive and simple polymerase chain reaction-single-strand polymorphism (PCR-SSCP) based method for detection of this genetic abnormality is reported. The study population consisted of 150 subjects whose factor V genotype was previously determined by PCR-RFLP method using the Mnl I restriction endonuclease. A 223-bp fragment containing the G1692-A (Arg 506-Gln) polymorphic site in exon 10 of the factor V gene was amplified, denatured, and run overnight on the commercially available GMA gels for SSCP. PCR-SSCP analysis showed reproducible and uniform band patterns for FV mutant and wild type alleles. Furthermore, PCR-SSCP results were consistent with those obtained with PCR-RFLP analysis (100%). The described PCR-SSCP procedure is reliable, time-saving, and cost-effective. The method may be considered as a potentially powerful new tool in the routine detection of factor V Leiden.