To identify the histologic and ultrastructural features of surgically excised subfoveal choroidal neovascular lesions from patients enrolled in the Submacular Surgery Trials and to compare them with clinical data. Surgically excised subfoveal choroidal neovascular lesions from patients enrolled in the Submacular Surgery Trials group N trial (lesion predominantly choroidal neovascularization [CNV] with evidence of classic CNV from age-related macular degeneration), group B trial (lesion predominantly hemorrhagic from age-related macular degeneration), and group H trial (idiopathic subfoveal CNV or subfoveal CNV from ocular histoplasmosis syndrome) between October 1, 1999, and September 1, 2001, were submitted to the pathology center. The lesion growth pattern (subretinal pigment epithelial [sub-RPE], subretinal, combined, or indeterminate) and the cellular and extracellular constituents were classified independently. Demographic, clinical, and fluorescein angiographic characteristics of patients, eyes, and lesions, respectively, were compared with the pathologic features. Of 269 patients assigned to surgery during the 24 months that pathologic specimens were collected, surgical specimens from study eyes of 199 were submitted to the pathology center. Of the 199 routine histologic specimens processed, 144 (72%) were classified as CNV, 51 (26%) as fibrocellular tissue, and 4 (2%) as hemorrhage. The median specimen size was smaller in group H (932 x 208 mum) than in groups N (1980 x 325 mum) and B (1800 x 395 mum). The CNV growth pattern was determined in 91 (46%) of 199 specimens. Of 159 group N and group B lesions, 76 (48%) had an indeterminate growth pattern, 28 (18%) had a sub-RPE growth pattern, and 33 (21%) had sub-RPE and subretinal growth patterns. Of 40 group H lesions, 32 (80%) had an indeterminate growth pattern, 7 (18%) had a subretinal growth pattern, and 1 (2%) had a combined sub-RPE and subretinal pattern. Based on electron microscopy, the most common cellular lesion components were RPE, macrophages, erythrocytes, fibrocytes, and vascular endothelium; the most common extracellular components were 24-nm collagen and fibrin. Basal laminar and linear deposits were found in 80% (40/50) and 16% (8/49) of group N specimens, 66% (43/65) and 5% (3/65) of group B specimens, and 8% (2/26) and 0% (0/26) of group H specimens, respectively. Most surgically excised subfoveal specimens had evidence of CNV or tissue associated with CNV. The constituents in CNV were consistent with granulation tissue proliferation. The presence of basal deposits in surgically excised specimens suggested a clinical diagnosis of age-related macular degeneration, even when blood was the predominant component of the lesion. Correlation of growth patterns above or below the RPE with fluorescein angiographic patterns of classic or occult CNV was limited because most specimens had insufficient material to determine these patterns.