This is the first report describing the syndrome of hypotony and ciliochoroidal detachment following pharmacologic aqueous suppressant therapy in previously filtered eyes. Four patients had a history of advanced primary open-angle glaucoma treated with multiple medical therapies, including timolol for 11 to 36 months. They then underwent filtration surgery, which failed in two cases. Timolol and/or acetazolamide therapy was instituted 1 to 18 months following surgery. The patients then developed hypotony and ciliochoroidal detachment, which resolved spontaneously after cessation of the pharmacologic aqueous suppressant therapy. In three of the cases, the episode of hypotony and ciliochoroidal detachment recurred after a second challenge with timolol and/or acetazolamide therapy. Inflammation, tumor, wound leakage, retinal detachment and cyclodialysis cleft were excluded. A mechanism of formation of ciliochoroidal detachment in this syndrome is proposed. Long-term timolol therapy followed by filtration surgery and its attendant postoperative hypotony and ciliochoroidal detachment sensitizes the ciliary epithelium. Subsequent pharmacologic aqueous suppressant therapy results in almost total reduction of aqueous production, causing hypotony and ciliochoroidal detachment.