Serologic testing is important in the evaluation of patients with autoimmune connective tissue diseases (CTD). There are many techniques. Each of the tests has different sensitivity and specificity with varying diagnostic value. These serologic tests detect antibodies to numerous cellular components. The diagnostic significance and specificity of each antibody vary. Choosing the appropriate test and understanding its clinical utility is an important aspect in the diagnostic evaluation of patients with CTD. (J Am Acad Dermatol 2000;42:159-74.) Learning Objective: At the conclusion of this learning activity, participants should be familiar with the various serologic tests for CTD, should understand the associations of specific antibodies with individual CTD, and should identify the factors that influence the predictive value of these serologic tests.