The histology of mouse secondary lymphoid tissue was examined following infection of Trichinella spiralis. ICR/CD-1 mice were orally infected with 200 T. spiralis and sacrificed at either 0, 3, 7, 14, 28 or 56 days after nematode administration. The animals were bled and sacrificed, and mesenteric lymph nodes were removed from each animal. They were fixed in 10% neutral buffered formalin, embedded in paraffin, and cut in 4-µm sections. Examination of serial sections demonstrated the sequential development of histological alteration in these regional lymph nodes. Hyperplasia was detected as early as 3 days after infection. Progressive changes occurring between 7 and 28 days after larval inoculation included hyperplasia with concurrent congestion of medullary sinuses, with increased numbers of neutrophils, histiocytes, lymphocytes, and eosinophils. Microscopic appearance of nodes removed from 56-day infected mice was similar to that noted for control tissues.