To better define Loa loa infection in the rhesus monkey and assess the potential usefulness of this host as a model for studies of human loiasis, 12 monkeys (four splenectomized and eight nonsplenectomized) were inoculated with L. loa infective larvae. Microfilaremia and hematologic changes as well as parasite-specific antibody were assessed as a function of time in these animals. Eleven of 12 inoculated monkeys became microfilaremic. Splenectomized animals had moderate (250–1,000) to low (< 250) numbers of microfilariae per milliliter (mf/ml), whereas the mf/ml in nonsplenectomized animals varied from high (> 1,000) to low. A significant increase in total leukocyte and lymphocyte numbers was seen in animals with moderate-to-low mf/ml but not in animals with high mf/ml mainly because of variations between animals in the latter group, rather than a direct consequence of increased mf numbers. All infected animals developed an eosinophilia before patency, suggesting the adult worms most likely contribute to this phenomenon. As the infection progressed, the eosinophil numbers decreased significantly. Although splenectomized animals overall had slightly higher numbers of total leukocytes (lymphocytes and eosinophils), these hematologic changes as a function of time were not significantly different from those in nonsplenectomized animals. Parasite-specific IgG antibody was increased significantly before patency in all animals and with the exception of the one amicrofilaremic animal, it decreased after patency. This study shows that splenectomy of rhesus monkeys prior to L. loa inoculation does not enhance the microfilarial density nor does it adversely affect eosinophilia or antibody production. Additionally, it appears that mf antigens and/or other undefined immunologic modulating factors may contribute to down-regulating eosinophil numbers and antibody production after onset of patency in these animals.