Three classes of inorganic solid acid catalyst have been demonstrated to be effective for methyl tert-butyl ether (MTBE) syntheses from methanol/tert-butanol (TBA) feed mixtures using a continuous, plug-flow, reactor system. These catalysts include heteropoly acids, such as 12-tungstophosphoric acid and 12-molybdophosphoric acid, on Group III and IV oxide supports, such as titania, HF-treated montmorillonite clays, as well as mineral acid-activated clays. Changes in the structure of the 12-tungstophosphoric acid-on-titania during etherification service have been investigated using P-31 and H-1 MAS NMR. An unexpected, in situ, phase separation of the desired MTBE plus isobutene products from aqueous methanol has been observed at high (>80%) tell-butanol conversion levels and operating temperatures greater than or equal to 160 degrees C. Milder etherification conditions allow MTBE selectivites to 94 mol% and sustained etherification activity for the HF/clay catalyst even with crude TEA feedstocks.