The activity of pergolide, a clavine ergolene, and mesulergine, an 8-alpha amino ergoline, were compared in 18 patients with advanced Parkinson's disease. All of the patients were no longer satisfactorily responding to levodopa, and 16 patients had diurnal oscillations in performance. Pergolide, mean dose 2.7 mg, when added to levodopa resulted in a significant (27%) decrease in Parkinson disability and a significant improvement in diurnal oscillations in performance (136% increase in hours 'on'). Twelve of the 18 patients (67%) improved. However, after 2 years pergolide was discontinued in all of the patients because of decreased efficacy, adverse effects, or both. At this time, mesulergine, mean dose 9.3 mg., when added to levodopa resulted in a significant (37%) decrease in Parkinson disability and a significant improvement in diurnal oscillations (61% increase in hours 'on'). Twelve of the 18 patients (67%) improved. Adverse effects (dyskinesias) were less with mesulergine than with pergolide. A declining response to one agonist does not preclude a successful response to another agonist of a different class.