This review discusses the interference in clinical chemical analysis caused by autoantibodies and by antibodies to foreign antigens. The nature of these disturbances, their occurrence, prevalence, and detection, the different ways in which they are manifested, the clinical consequences of the failure to recognize such interference, and finally methods for avoiding these disturbances are discussed. Interference by cold agglutinins in the automatic determination of the erythrocyte count, interference by cryoglobulins in the determination of the leukocyte count, and EDTA-induced thrombocyte agglutination are well documented as sources of error in the analysis of haematological parameters. Enzyme determinations may be affected by the occurrence of macro-complexes of the measured enzyme with immunoglobulins. This type of interference, for example, may occur in the determination of amylase and creatine kinase. Immunoassays for the determination of hormones or tumour markers are sensitive to autoantibodies and heterophilic antibodies. The former are particularly important in the determination of thyroid hormones, where the interference is method-dependent. In several immunoassays, interference by heterophilic antibodies can be abolished by the addition of non-immune serum. Finally, rheumatoid factors, antibodies administered for therapeutic purposes, and monoclonal gammopathies are possible sources of interference in the determination of various analytes.