Three fragments of cruzipain, expressed separately in bacterial vectors, were used to detect antibodies in sera from patients with chronic Chagas' disease. Most antibodies directed against the enzyme were found to react with the C-terminal extension, thus suggesting the presence of immunodominant B-cell epitopes within this protein domain. Immunoprecipitation with these antibodies did not impair enzyme activity. It is suggested that cruzipain consists of an enzymatic domain and a non-enzymatic, immunodominant domain, which corresponds to the C-terminal extension.