In recent years, bovine Onchocerca species have been used as models for human onchocerciasis in drug screens. They have been suggested for immunology studies and evaluation of vaccine candidates. Therefore, mast cells and their association with other inflammatory cells were studied in five onchocercal species of cattle and deer using immunohistology. Intact mast cells occurred in large numbers in the capsule and septae of nodules, in fibrous tissue adjacent to nonnodular worms, and perivascularly. Inactive and, more frequently, activated and degranulating mast cells were observed within infiltrates in the nodule center or around nonnodular filariae. They were not detected in direct contact with the cuticle of adult worms or of microfilariae or among the macrophages, giant cells, and neutrophils forming the innermost layer around the worms. Eosinophils, but not mast cells, were obviously associated with microfilariae producing females. The distribution, frequency, and activity of mast cells were similar for all five species and O. volvulus.