Drusen in the macular area may precede other manifestations of age-related macular disease associated with severe visual loss. To identify fundus changes that might be predictive of advanced age-related maculopathy, we examined 79 patients with drusen for up to 3 years. Fundus photographs and fluorescein angiograms were independently analysed by two readers in a masked fashion using a standardized grading scheme. Fourteen patients (17.7%) developed a new exudative or nonexudative lesion involving the fovea. Delayed choroidal perfusion on the fluorescein angiogram, interpreted as an indicator for diffuse thickening of Bruch's membrane and relative atrophy of the choriocapillaris, was observed in 12 patients, 5 of whom developed geographic atrophy of the retinal pigment epithelium during follow-up (P < 0.009). Additional predictive characteristics included focal hyperpigmentations (P < 0.005) and focal extrafoveal areas of atrophy of the retinal pigment epithelium within 1600 microns of the center of the fovea (P < 0.031). These ocular features allow identification of patients with macular drusen at high risk for the development of complicating macular lesions.