Lazabemide (Ro 19-6327) is a relatively short-acting, reversible, and selective type B monoamine oxidase inhibitor that is not metabolized to amphetamines or other active compounds. We previously found lazabemide to be safe and well tolerated at dosages of up to 400 mg/day during a 6-week study of 201 patients with early untreated Parkinson's disease (PD). We now assess whether or not lazabemide influences the progression of disability in untreated PD. Patients (N = 321) were assigned by randomization to one of five treatment groups (placebo, 25 mg, 50 mg, 100 mg, or 200 mg/day) and followed systematically for up to 1 year. The risk of reaching the primary end point (the onset of disability sufficient to require levodopa therapy) was reduced by 51% for the patients who received lazabemide compared with placebo-treated subjects. This effect was consistent among all dosages. The frequency of adverse experiences did not differ among the treatment groups. At dosages ranging from 25 to 200 mg/day, lazabemide was well tolerated and delayed the need for levodopa in early, otherwise untreated PD. The magnitude and pattern of benefits were similar to those observed after 1 year of deprenyl (selegiline) treatment in the DATATOP clinical trial.