Protein C deficiency is an autosomally inherited disorder that is associated with a high risk of recurrent venous thrombosis. The authors have shown that temperature gradient gel electrophoresis (TGGE) is a simple and rapid screening method for the detection of mutations in the protein C gene. Samples from eleven patients with sequence defined point mutations in the promoter region of exon I, and in exons II, III, VII, VIII and IX were analysed by TGGE. In all cases the mutations were readily detected. The exons IV, V and VI were not submissive to TGGE analysis due to amplification difficulties. However, specific computer calculations predict a more general applicability of TGGE for the detection of any mutation in the protein C gene. The presented data establish the usefulness of TGGE as a simple and rapid screening method for the detection of hereditary mutations in the protein C gene.