A retrospective study was undertaken in Recife, Brazil to evaluate the specificity of intrascrotal nodules detected by physical examination as a marker of dead or degenerating adult Wuchereria bancrofti worms (filarial granuloma). A total of 372 nodules from 340 adult male patients (mean age 23.1 years) were studied. Of those, 253 (68%) nodules were from 226 patients treated with antifilarial drugs (Group 1) and 119 (32%) nodules were considered non-drug related and were obtained from 114 patients (Group 2). On histologic examination, all nodules from Group 1 and all but one (99.1%) from Group 2 contained degenerated or dead adult worms. In the one case without filarial granuloma, ectopic cortical adrenal tissue was found in the spermatic cord. These findings emphasize the high specificity of intrascrotal nodules for bancroftian granuloma and draw attention to the importance of examining the scrotal contents of young men in studies of antifilarial drug efficacy. These findings also have potential implications for bancroftian filariasis control programs.