IgA-class antiendomysium antibodies (IgA-EmAs) are a very sensitive and specific serological marker of celiac sprue. Using an indirect immunofluorescent method, we evaluated the kinetics of the antibody titers both during a gluten-free diet and after gluten was added, comparing them with the intestinal histological pattern. The IgA-EmA titers were evaluated on sera from 91 untreated adults with biopsy-proven celiac sprue and, when positive, were reappraised after different durations of gluten-free diet. Antibody titers were also retested in eight adolescents who had voluntarily discontinued the diet while they were on a free diet. The IgA-EmAs were detectable in 85 of 91 (93.40%) patients but in none of the 438 controls (100% specificity). The antibody titers ranged from 1:5 to 1:2,000 or more and the intestinal histopathological pattern paralleled the antibody titers. After gluten withdrawal, IgA-EmA titers declined to zero in all patients complying with their diet. Modifications in gut histopathologic condition paralleled IgA-EmA kinetics, although seroconversion to negativity preceded mucosal recovery. After a gluten rechallenge, deterioration in gut histopathologic condition followed EmA reversion to positivity. Three negative IgA-EmA tests did not reflect a worsening in gut histopathologic condition after a gluten-containing diet, thus making the diagnosis of celiac sprue uncertain.