Pergolide is a potent dopamine agonist and is known to have anti-Parkinson properties. We administered pergolide to patients with suboptimal control of Parkinson's disease who had a short-duration response to carbidopa-levodopa in a 6-month, double-blind study. Pergolide added to the carbidopa-levodopa regimen resulted in both subjective and objective improvement in comparison with placebo. In patients who tolerated pergolide, the median time spent in the "off" (parkinsonian) state was reduced from 5.0 to 2.2 hours daily (compared with a 0.3-hour reduction in the placebo group). These patients were able to decrease the median frequency of carbidopa-levodopa dosage from 7.5 to 5.0 doses daily (no change in the placebo group). Prolongation of the "on" response (optimal response to treatment) to single doses of drugs was corroborated by monitoring of the patients' Parkinson response cycle. The peak response was also improved in most patients. Of 25 patients randomized to the pergolide group, 7 were unable to tolerate this drug; confusion or hallucinations occurred in 4 of these patients, and chest pain, leukopenia, and nonspecific dizziness, respectively, developed in the other 3. All adverse events were reversible with reduction of the dose or discontinuation of the pergolide regimen. In conclusion, patients with Parkinson's disease who experience clinical fluctuations with carbidopa-levodopa may be helped by the addition of pergolide to the therapeutic regimen.