Two young patients with unimpaired renal and hepatic function were found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of salicylates and carbonic anhydrase inhibitors in normal doses. Carbonic anhydrase inhibitors appear to interact with salicylates to produce serious metabolic acidosis in patients without the predisposing factors generally considered to constitute risks. It is recommended that treatment combining salicylates and carbonic anhydrase inhibitors is either kept to a minimum or avoided.