Five functional assays and two immunoassays for protein C (PC) were evaluated in parallel for the same plasma samples collected from healthy subjects, patients with congenital and acquired PC deficiencies or patients with conditions associated with high PC levels. For 7 patients starting warfarin therapy and for 15 patients during stabilized warfarin therapy, there were significant between-assay differences. For these groups immunoassays gave higher values than most functional assays and the latter also gave varied results, probably depending on their respective capacity for recognizing a carboxylated PC. On the other hand, there were no significant between-assay differences nor discrepancies between PC activity and antigen levels for healthy subjects (n = 39), patients with congenital PC deficiency (n = 10), myocardial infarction (n = 25), chronic liver disease (n = 19), disseminated intravascular coagulation (n = 35), in the post-operative period (n = 20) or in women taking oral contraceptives (n = 20). This comparison of PC assays indicates that PC levels measured by different functional or immunological assays are very close in the majority of clinical conditions, but not for patients on oral anticoagulants.