The congenital deficiency of prekallikrein (PK) is a rare condition in which there is a peculiar discrepancy between a severe in vitro defect and absence of bleeding. The gene controlling PK synthesis is located on chromosome 4 and consists of 14 exons and 15 introns. Only approximately 80 cases of PK deficiency have been described in the literature. Owing to the lack of bleeding, most cases go undetected or, if detected, go unreported. Occasional bleeding or thrombosis have been reported in a few patients but this was only due to the presence of associated risk factors. It is certain that the defect does not protect from thrombosis. Diagnosis is based on the presence of a great prolongation of partial thromboplastin time and normal prothrombin time and thrombin time. The long partial thromboplastin time is fully corrected by the addition of normal plasma or normal serum and presents the unusual feature of shortening on long incubation times. Platelet and vascular tests are normal. Immunological studies allow differentiation into two types, namely cases of true deficiency, which are approximately 70% of the total, and cases with abnormal forms. PK is a glycoprotein synthesized in the liver as a single-chain peptide of 88000 Da. It mostly circulates (∼75%) as a complex with high-molecular-weight kininogen. It is cleaved by FXIIa into a heavy chain and a light chain (catalytic domain), held together by disulfide bonds. Molecular biology techniques have so far only been applied to eleven families, and these studies do not yet allow definite phenotype/genotype conclusions. The exons involved are 5, 8, 11, 14 and 15. The noncoagulative effects of PK, mainly based on the effect of kallikrein, have been studied less, since they appear to be the result of the involvement of other components of the contact phase. Kallikrein can mainly affect the formation of bradykinin from high-molecular-weight kininogen and the activation of pro-urokinase to urokinase. Bradykinin causes inflammation, vasodilatation and an increase in vessel permeability. The activation of pro-urokinase results in enhanced fibrinolysis. However, fibrinolysis has been reported to be normal or defective in these patients.