Reaction kinetics measurements, selective poisoning, and microcalorimetry were used to study the activity, selectivity, and deactivation of acid sites on a sulfated zirconia catalyst for n-butane isomerization at 423 K. The sulfated zirconia catalyst has a distribution of acid site strengths, containing 50 mu mol/g of strong acid sites characterized by heats of ammonia adsorption from 125 to 165 kJ/mol. The strongest acid sites (heats from 145 to 165 kJ/mol) are responsible for the high initial activity of the catalyst, but these sites deactivate rapidly under reaction conditions. The acid sites exhibiting heats from 125 to 145 kJ/mol are less active than the stronger sites, but deactivate more slowly. Weaker sites have low activity and deactivate more rapidly after the intermediate sites are deactivated or poisoned. Bronsted acidity is necessary for extended catalytic activity, although Lewis acid sites may play a role in generating the initial high activity. Acid sites with heats of ammonia adsorption from 125 to 165 kJ/mol show good selectivity for production of isobutane (ca. 93%), while sites with heats from 120 to 125 kJ/mol show lower isobutane selectivity (ca. 80%).