A patient had a 12-year history of relapsing disseminated histoplasmosis. None of the characteristic lesions of the presumed ocular histoplasmosis syndrome were present in either eye. Ocular involvement began as a peripheral focal retinitis associated with vitreitis and iritis. Histoplasma capsulatum organisms grew in cultures from aqueous and vitreous and were demonstrated histologically in an iridectomy specimen. Despite intraocular and subconjunctival administration of amphotericin B, intractable pain associated with progressive necrotizing granulomatous iridocyclitis necessitated enucleation. Histoplasma capsulatum organisms were seen extracellularly in the vitreous cavity and both intracellularly and extracellularly in areas of granulomatous inflammation involving the iris, ciliary body (diffusely), and the retina (focally). The choroid was not involved.