The sequential lymphoreticular lesions of canine neorickettsiosis caused by Neorickettsia helmintheca (NH), the Elokomin fluke fever agent (EFF), and a mixed inoculum containing both agents were studied. Morphologic changes of greatest severity were found in NH-infected dogs 13 days after inoculation. These changes included severe depletion of small lymphocytes from the lymph node cortex and loss of germinal centers concurrent with marked infiltration of macrophages. Splenic follicular necrosis and obliteration of thymic architecture by infiltration of macrophages were also distinguishing lesions. The distribution and concentration of NH antigen were similar to those of EFF antigen during development of lesions, as determined by fluorescent antibody examination. The disappearance of EFF preceded the regression of macrophage infiltration, suggesting that factors other than organisms were responsible for macrophage infiltration.