The distribution of the oxidation polymorphism related to cytochrome CYP2D6 (debrisoquine type) was determined in 246 healthy Italian volunteers. Phenotyping was based on HPLC determination of the dextrometorphan/dextrorphan concentration ratio (metabolic ratio) in urine samples collected over an 8 h interval following a single oral 30 mg dose of dextromethorphan hydrobromide. Urinary excretion of dextromethorphan showed a wide interindividual variability, ranging from < or = 0.04 to 3.9% and from 0.5 to 79.6% of the dose, respectively. Metabolic ratios ranged from < or = 0.001 to 6.6. Eleven of the 246 subjects showed a metabolic ratio greater than 0.30, indicating that 4.5% of the population could be ascribed to the poor metabolizer status. The frequency of the poor metabolizer phenotype in this population is within the range described for other Caucasian ethnic groups.