PURPOSE: To describe two cases of neovascular age-related macular degeneration (AMD) that progressed despite a single intravitreal injection of pegaptanib sodium (Macugen) six weeks earlier. DESIGN: Interventional case report. METHODS: A 62-year-old man and a 76-year-old woman with occult and minimally classic lesions, respectively, each received a single injection of intravitreal pegaptanib. RESULTS: Within six weeks of an intravitreal pegaptanib injection, the choroidal neovascularization (CNV) progressed. In one eye, the chronic occult lesion developed subfoveal classic CNV. In the other eye, the classic component of the minimally classic lesion tripled in size. CONCLUSIONS: A single dose of intravitreal pegaptanib was not effective in these two patients at six weeks. This report reminds the ophthalmologist to consider obtaining a fluorescein angiogram during follow-up after an intravitreal pegaptanib injection to monitor CNV lesion characteristics, particularly if the visual acuity decreases.