We compared the results of treatment with selegiline (deprenyl, Eldepryl) in 17 patients with advanced Stage 4 Parkinson Disease (PD) who were on levodopa (as Sinemet) with 65 Stage 2 or 3 patients with early PD who were also on levodopa. The first group consisted of 17 patients with advanced Stage 4 PD without response fluctuations ("wearing off" or "on off" phenomena). Their mean age was 72.1 +/- 7.5 years, their mean duration of PD was 7.4 +/- 3.2 years. The second group consisted of 65 patients with Stage 2 or 3 PD who had recently been started on levodopa. Their mean age was 63 +/- 12.1 years, their mean duration of PD was 7.4 +/- 3.2 years. The mean dose of selegiline was 10.0 +/- 1.8 mg per day (range 5-20 mg). The mean duration of treatment was 1.5 +/- 0.8 years. During the four years of observation 55.3 +/- 8.0% of the Stage 2 or 3 patients improved while only 14.3 +/- 13.5% of the Stage 4 patients improved. This difference was significant (p less than 0.05). During this time 22.0 +/- 6.7% of the Stage 2 or 3 patients worsened and 60.7 +/- of the Stage 4 patients worsened. This degree of worsening was significant (p less than 0.05). Adverse effects were minor and reversible. Our observations suggest that selegiline is more effective (higher percent of patients improving, lower percent of patients worsening) when it is added earlier with patients on levodopa than when it is added later.