The environment of ionizable groups in 36 proteins is characterized in terms of solvent-accessibility, salt-bridge formation and hydrogen-bonding. Possible implications of our results as to the protonation state of buried ionizable groups are considered and patterns useful for model building studies on proteins are derived. The most interesting finding is that there are on average two completely buried ionizable groups per protein of which at least 20% do not form salt-bridges. However, all buried ionizable groups form hydrogen bonds with neutral polar groups.