In a double-masked, 3-month clinical study the ocular hypotensive effects of diacetyl nadolol (DAN), timolol, and nadolol were compared. When applied topically to the eyes of glaucomatous patients timolol 0.5% was found to be significantly more effective than DAN 2% in controlling IOP at 3 of 10 evaluation periods. Fewer patients, however, developed tolerance to DAN 2% than to timolol 0.5%. DAN 0.5% was also effective in lowering intraocular pressure in 3 of 8 patients tested. Nadolol 2% had no long-term ocular hypotensive effect. Two of 8 patients treated with DAN 2% developed a bilateral periorbital dermatitis and were removed from the study even though their intraocular pressures were well controlled. No other clinically significant local or systemic side effects were observed during the course of the study.