Six patients with evidence of secondary syphilis presented with visual loss in both eyes caused by large, placoid, yellowish lesions with faded centers at the level of the pigment epithelium in the macula and juxtapapillary areas. All eyes had vitreitis. All of the lesions showed a similar fluorescein angiographic pattern of early hypofluorescence and late staining. Five patients had mucocutaneous lesions typical of secondary syphilis. All five patients treated with antibiotics had prompt improvement in visual function and resolution of the fundus lesions. The ophthalmoscopic and angiographic appearance of these posterior fundus lesions was sufficiently characteristic to suggest a diagnosis of secondary syphilis. Modification of the host response to syphilis by human immune deficiency virus (HIV) infection may be partly responsible for this peculiar fundus picture. Three of the four patients tested positive for HIV.