This is the first reported clinicopathologic correlation of focal photocoagulation treatment in a diabetic patient treated as part of the Early Treatment of Diabetic Retinopathy Study (ETDRS). Twenty focal argon laser burns were evaluated clinically in their acute and chronic stages, and histopathologically more than 3 years after exposure. Damage profiles of the lesions were reconstructed from serial tissue sections. In single burns the outer nuclear layer defect measured 78 +/- 31 microns, in confluent burns 257 +/- 73 microns. Inner nuclear layer defects were present only in lesions that clinically, during their acute stage, showed a white center or a white collar around the treated target. Fibrous subretinal and subpigment epithelial membranes extended from the burn centers for a distance of up to 900 microns and contained Müller cell processes as identified by immunostaining. These findings confirm the empirical rationale of current focal treatment, but also, because of the apparent risk of membrane formation, urge caution when treating close to the fovea.