To evaluate the autofluorescence findings of acute syphilitic posterior placoid chorioretinitis (ASPPC). Patients with ASPPC underwent complete ophthalmologic examinations, including biomicroscopy, fundus color photography, autofluorescence photography, and fluorescein angiography. As expected, the patients had a yellowish lesion in the posterior pole. However, the lesion appeared to have two components, a diffuse placoid yellow discoloration at the level of the retinal pigment epithelium (RPE) and focal yellow spots that appeared to lie on the RPE. The diffuse placoid yellow color change at the RPE level showed a slight generalized increase in autofluorescence admixed with tiny spots of decreased autofluorescence. The yellow collections in front of the RPE were intensely hyperautofluorescent. The placoid area showed fluorescein staining, while the yellow deposits blocked the background fluorescence. Treatment of syphilis caused resolution of the placoid changes with associated improvement in the autofluorescence and fluorescein abnormalities. Patients with ASPPC have autofluorescence abnormalities during the acute manifestations of the disorder that help in interpretation of the fluorescein angiographic findings. We found evidence that the RPE is primarily involved and there does not appear to be choriocapillaris occlusion in early lesions.