This open-label phase I trial assessed potential pharmacokinetic interactions between oral levodopa/carbidopa and transdermal rotigotine treatment at steady state. Twenty-four participants with idiopathic restless legs syndrome (12 per group) received levodopa/carbidopa (100 mg/25 mg bid) and rotigotine (initial dose 2 mg/24 h for 3 days, followed by 4 mg/24 h) in a randomized sequence as monotherapy and in combination during hospitalization for 13 days. Primary pharmacokinetic parameters were AUC(ss) and C(max,ss) of levodopa, carbidopa, and rotigotine at steady state. Mean concentration-time profiles of the 3 agents were similar during monotherapy and combination treatment. The point estimate for the ratio of geometric means (combined vs monotherapy) for AUC(ss) and C(max,ss) for levodopa (0.98 and 1.04), carbidopa (1.03 and 1.06), and unconjugated rotigotine (1.02 and 0.98) was near unity. All 90% confidence intervals were within the acceptance range for bioequivalence (0.8, 1.25). The most frequently documented adverse events were application site reactions (itching and reddening at application site) and headache. Most adverse events were mild to moderate in intensity, but 2 were of severe intensity (headache and extrasystoles); no serious adverse events occurred. The data presented indicate that rotigotine and levodopa/carbidopa can be coadministered without pharmacokinetic interactions between the compounds.