The effect of levodopa on the externally recorded preejection period (PEP), blood pressure, and heart rate was evaluated in patients with Parkinson's disease during the first 2 weeks of therapy and after 3 months of continuous therapy. During the same time periods, the response of these parameters to graded intravenous doses of dopamine and epinephrine was determined. During the first 2 weeks, levodopa (1.0 and 1.5 g) produced a dose-related shortening of the PEP which was maximal at the time of the 30 or 60-min recordings and remained significant (P< 0.05) for 90 min following the 1.0-g dose and for 120 min after the 1.5-g dose. The drug had no effect on heart rate and reduced arterial blood pressure minimally. Propranolol (10 mg by mouth) prevented the shortening of PEP produced by levodopa. After 3 months of therapy, levodopa (1.5 g) failed to shorten the PEP significantly. However, the effect of dopamine and epinephrine on PEP was not significantly different from that obtained during the first 2 weeks of treatment with levodopa. It is concluded that levodopa exerts a positive inotropic effect which is mediated via beta-adrenergic receptors and that tolerance develops by 3 months of continuous administration. The tolerance does not appear to be caused by impaired responsiveness of the heart since the effect of graded doses of dopamine and epinephrine on the PEP was similar during both acute and chronic administration.