SUMMARY The sensitivity of methods to detect antibodies to intrinsic factor was assessed. Five sera of known antibody content were tested in 31 laboratories and 30 sera from patients with pernicious anaemia were tested in one laboratory. Five non-commercial methods and two kits for type I antibodies and one non-commercial method for types I and II antibodies are in current use. Differences in sensitivity of the non-commercial methods for type I antibodies related more to the antigen:antibody ratio in the test system than to the method itself. A radioimmune assay for types I and II antibodies showed the best sensitivity but that of an enzyme linked immunosorbent assay (ELISA) method was poor Type I antibodies (IFA) to intrinsic factor, which block the binding of cobalamin to intrinsic factor, have been recorded in the 31% to 76% ofpatients with pernicious anaemia.' This large variation may be due to case selection or to differences in technique used, or both. Because the detection ofIFA may avoid the need for further investigation in the diagnosis of pernicious anaemia we compared the sensitivity of some of the methods in current use, including two which detect type II antibodies (inhibitors of the attachment of intrinsic factor to the ileal mucosa) at the same time. Tests for type II antibodies alone are not often used because the antibodies are thought to be less common than type I antibodies, though this may not be so.2 Material and methodsSera were collected from patients with pernicious anaemia and from a healthy control. These were coded and sent to laboratories which undertake IFA testing and which had agreed to test samples for us. Two sera from patients with pernicious anaemia containing, respectively, 6 and 2 units IFA/ml were issued first and on a second occasion, patients' serum containing 10 units IFA/ml together with this serum diluted by a factor of 8 and 10 in the normal serum, and the normal serum were sent.