Dopaminergic stimulation by apomorphine causes severe adverse effects such as vomiting and sedation. We compared the effectiveness of the serotonin 5-HT(3) antagonistic antiemetic drug ondansetron in a single oral dose with the standard regimen using domperidone TID 2 days prior to stimulation. In a double blind, randomised parallel group design, 16 previously untreated Parkinsonian patients were investigated, eight patients received domperidone (total dose 140 mg, starting 2 days prior to apomorphine challenge) and eight patients ondansetron (8 mg single dose 2 hr prior to investigation). Adverse events following the injection of 2-3 mg apomorphine were rated on a four-item scale. In an overall analysis, dopaminergic stimulation was significantly better tolerated, if the patients received domperidone, whereas more severe adverse effects were noted after ondansetron. Following ondansetron pre-treatment, seven patients experienced marked nausea or vomiting, all patients yawned, six patients had marked sedation, two patients a blood pressure decrease of more than 20 mmHg, and four patients strong sweating. In contrast, the latter side effect was found only in one patient pre-treated with domperidone, no patient had significant blood pressure decrease, all patients yawned, and seven domperidone patients had slight nausea. We conclude that oral ondansetron is no alternative to domperidone in the pre-treatment regimen of dopaminergic stimulation.