The response to continuous intravenous infusion of levodopa was evaluated in 23 
patients with Parkinson's disease complicated by motor fluctuations. Conversion 
from oral to intravenous levodopa treatment resulted in an immediate and 
sustained stabilization of plasma levodopa levels in both the wearing-off and 
on-off groups. Motor variability also diminished within the first 24 hours of 
infusion, although to a much greater extent in patients with the wearing-off 
phenomenon. Over the next 5 to 11 days of intravenous treatment, further 
reductions in motor fluctuations occurred in both groups, at a substantially 
faster rate in the wearing-off group than in the on-off group. The degree of 
immediate stabilization of parkinsonian motor response correlated best with 
disease duration, whereas the rate of subsequent improvement correlated most 
closely with levodopa dose. The results support the view that the wearing-off 
phenomenon may reflect the degeneration of dopamine terminals as a consequence 
of natural disease progression with a resultant inability to buffer variations 
in levodopa availability; the on-off phenomenon may reflect additional 
postsynaptic changes, possibly occurring in response to the nonphysiological 
fluctuations in synaptic dopamine, which gradually remit during continuous 
levodopa administration.