The oral tyramine pressor test was administered to healthy males during treatment with a selegiline transdermal system (STS; 6 mg/24 h). The tyramine sensitivity factor (TSF) was calculated from the ratio of baseline and on-treatment tyramine pressor doses. The tyramine sensitivity factor value following 9 days of treatment with the selegiline transdermal system was 1.85 ± 0.10. Extended treatment, 33 days, produced a small, clinically nonmeaningful increase in this value. The tyramine sensitivity factor for the selegiline transdermal system was similar to that following treatment with 10 mg/d of oral selegiline capsules but more than 20 times less than observed during tranylcypromine treatment. A larger increase in the tyramine sensitivity factor was observed following extended selegiline transdermal system treatment at a higher dose (12 mg/24 h), which was significantly decreased following coadministration of tyramine capsules with a meal. These results suggest a wide tyramine safety margin for the selegiline transdermal system and provide evidence that the 6-mg/24-h selegiline transdermal system can be administered safely without dietary tyramine restrictions.