The pathogenesis of "random" fluctuations in parkinsonian mobility, which are not clearly related to the dosing schedule of levodopa, has not been determined. We rated parkinsonian mobility and assayed plasma dopa in one patient with clinically random fluctuations during two modes of administration of levodopa/carbidopa: (1) standard oral route and (2) direct duodenal delivery via nasoduodenal tube. During oral therapy, mobility varied unpredictably in relation to levodopa dosing, suggesting a clinically random pattern. During duodenal delivery, however, a predictable and dramatic pattern of recurrent end-of-dose deterioration was observed; each intraduodenal levodopa dose resulted in 60 to 90 minutes of benefit. Plasma dopa levels correlated closely with mobility ratings for both modes of administration. Our findings indicate that erratic gastric emptying of levodopa is responsible for apparently "random" oscillations in mobility in at least one patient with Parkinson's disease and probably in others.