We conducted a prospective, nonrandomized study in healthy volunteers to determine if racial differences exist in orosomucoid (ORM) and its variants, and to examine quinidine and lidocaine binding to the protein. Total ORM serum concentrations were measured by Laurell-Rocket immunoelectrophoresis. Allele types were determined by isoelectric focusing and immunoblotting. Total and unbound quinidine and lidocaine concentrations were measured with standard fluorescence polarization immunoassays after ultrafiltration. The frequency of the common ORM alleles was similar between 38 Caucasians and 67 African-Americans. Mean total ORM concentration was significantly lower in Caucasians (57.3 +/- 25.4 vs 73.2 +/- 33.9 mg/dl, p=0.01). However, more Caucasians took oral contraceptives, which may have decreased ORM concentrations. Quinidine unbound fraction (UF) was related to ORM phenotype. The highest UF was found with ORM 1-S (p=0.009). There were no significant relationships between ORM phenotype and lidocaine UF. Overall, African-Americans had higher ORM concentrations than Caucasians. Quinidine binding showed significant relationships to specific ORM variants.