The authors have investigated histologic and organ weight changes in the spleens of jirds (Meriones unguiculatus) experimentally infected with subperiodic Brugia malayi and two related species. A total of 214 infected animals were examined between 1 and 700 days post-inoculation: 50 females with B. malayi, 63 males with B. malayi, 51 males with B. pahangi and 50 males with B. patei. The low splenic indices and lack of histologic reactions other than moderate lymphoid hyperplasia during the first 2 mo post-inoculation suggested that, for the most part, splenomegaly was not associated with the decline in whole body worm recoveries which occurs during this interval. At about the end of the prepatent period, spleen weight increased in many jirds. Except among males infected with B. patei, mean splenic indices attained much of their full mean value by the end of the 4th month. B. malayi roughly doubled the normal splenic index, while B. pahangi caused some additional enlargement; B. patei infections yielded erratic but much larger indices. Histologic sections showed expansion of both red and white pulp; maximum follicular activity was observed in the 3rd and 4th months post-inoculation and gradually waned in long-term infections. Plasma cell infiltrates were conspicuous in some long-term infections and amyloidosis developed in a single B. patei spleen. Granulomatous foci associated with microfilariae in tissue were a conspicuous feature of B. pahangi infections. These lesions were also seen in B. patei infections but not among those infected with B. malayi. Although no consistent relationship was established between splenic reaction and level of microfilaremia, the persistence of elevated splenic indices was interpreted as a response to the production of microfilariae and to chronic antigenic stimulation by excretory or secretory materials.