a,-acid glycoprotein (AAG) concentrations and propranolol binding were investigated in the serum of elderly hospitalized patients with acute illness, and healthy elderly and young subjects. Significantly greater AAG concentrations and reduced unbound propranolol fraction were observed in the elderly with acute disease compared to the elderly controls. The greatest changes (up to five-fold) occurred with cancer, with lesser changes associated with myocardial infarction and ischaemic heart disease, acute infection, heart failure, chronic obstructive respiratory disease, and cerebrovascular accident. Various miscellaneous conditions were also associated with high AAG concentrations and enhanced propranolol binding. The healthy elderly had higher AAG concentrations and lower unbound propranolol fractions than the healthy young group. Overall there was a highly significant correlation between the propranolol binding ratio (bound/free) and the serum AAG concentration. These results suggest that the elderly population may be particularly susceptible to changes in AAG concentrations, and that during acute illness interpretation of serum concentrations of drugs which bind mainly to AAG, may require knowledge of their free fractions.