The sonographic evaluation of lymph nodes is based primarily on evaluation of their shape and size. Recently, however, the availability of high-frequency transducers has made consideration of internal structure possible. An important objective is to determine whether node enlargement is due to inflammatory or neoplastic processes. To determine the accuracy of sonography for this purpose, we obtained in vitro sonograms of 53 enlarged lymph nodes excised from 41 patients during surgery for neoplastic or nonneoplastic disease. The sonograms were obtained with 7.5- and 10-MHz transducers. They were interpreted by a radiologist who was unaware of the clinical diagnosis. The nodes were subsequently processed for anatomohistologic study; findings were compared side by side. In 26 of the 53 nodes, sonograms showed an identifiable central echogenic line, which on histologic specimen corresponded to the internal part of the medulla where the lymphatic sinuses converge. All these nodes were benign. Two other nodes had an echogenic internal structure not resembling the normal hilum; in one case this was caused by metastatic disease and in the other by fibrosis. Sonograms of the remaining 25 nodes showed no detectable hilar structure; 21 were involved by a tumor and four had diffuse fatty replacement. Our results suggest that the sonographic finding of a central echogenic line is a valid criterion of benignity. Absence of this finding may be due to factors other than neoplastic disease, such as fatty replacement.