Guinea pig inclusion conjunctivitis, a naturally occurring chlamydial disease of guinea pigs, resolves spontaneously after 3 to 4 weeks. The factors responsible for curbing the infection have not yet been specifically defined. Since Iwata (Invest. Ophthalmol. 15:297-301, 1976) reported cytochemical activity for peroxidase in the conjunctival epithelium of the normal rat, we undertook these studies to determine whether a similar activity exists in the guinea pig, and if so, whether it functions in the elimination of this Chlamydia psittaci infection. Tarsal conjunctivas of 14 normal guinea pigs, 34 infected ones, and 7 control guinea pigs (inoculated with yolk sac only) were excised and tested for peroxidase by the Graham and Karnovsky method (J. Histochem. Cytochem. 14:291-302, 1966). We found that peroxidase activity, virtually absent in normal animals, was intensely stimulated by the infection. This enzymatic activity appeared 2 days after inoculation of the conjunctiva with chlamydia and persisted for 6 to 7 weeks. The enzyme was localized in the rough endoplasmic reticulum and perinuclear cisternae of all layers of the conjunctival epithelium from the external surface to the basal lamina, including cells with no apparent inclusions as well as those heavily parasitized. Reaction in the Golgi complex was variable. No reaction, however, was ever evident in the chlamydial vacuoles or lysosomes, and the organisms continued to grow and multiply during peak enzymatic activity. We therefore concluded that the stimulated enzyme is apparently not directly responsible for the waning of the infection, but instead reflects an alteration of host metabolism that occurs as a consequence of the infection.