Clinicians use acute challenges with levodopa (LD) and/or apomorphine (A) for diagnostic dopaminergic response tests in Parkinson's disease (PD) patients. We consecutively compared the value of both drugs with performance of repeated ratings and adverse effect recording. Oral administration of 200 mg LD was superior to subcutaneous injection of 4 mg A in terms of tolerability and onset of temporary UPDRS motor score decline ([previously untreated PD patients] LD: 4.02 [mean] +/- 2.45 [SD] [significant decrease: p = 1.42 E-07] vs. A: 1.58 +/- 3.38 [not significant decrease: p = 0.14], p = 0.0009; [treated PD patients] LD: 7.71 +/- 4.35 [significant decrease: p = 2.48 E-06] vs. A: 5.19 +/- 4.32 [significant decrease: p = 7.83 E-05], p = 0.07). We suggest diagnostic acute challenge test performance with LD as first- and A as second choice due to better tolerability and valuation in combination with repeated scoring procedures to improve sensitivity and specifity.