Immune complex mediated damage, still incompletely understood, is a frequent and important pathogenetic mechanism in several major rheumatic diseases. Injury by circulating immune complexes seems to be related mainly to the size of the complexes and their ability to activate the complement system. The more circulating immune complexes are looked for to assess the nature of an activity of diseases, the more clinicians are faced with difficulties in interpretation. This is partly because of rapidly increasing number and types of immune complex assays and the conflicting data obtained. An understanding of the principles behind the commonly used immune complex assays allows the clinician to appreciate their advantages and weak points and to apply them correctly in investigating the clinicopathological aspects of immune complex mediated rheumatic diseases.