A randomized, cross-over study was designed to compare the effects of an increased ratio (from 1:10 to 1:4) of carbidopa to levodopa on the fate of levodopa and carbidopa in 11 healthy subjects. Four combinations of carbidopa/levodopa (10 mg/100 mg, 25 mg/100 mg, 25 mg/250 mg, 62.5/250 mg) were used. Plasma levodopa, carbidopa, dopamine and dopac concentrations as well as urinary excretions of levodopa and dopac were determined by a sensitive high-performance liquid chromatography with electrochemical detection after a single carbidopa/levodopa tablet. As the ratio of carbidopa to levodopa increased, there was a significant increase in apparent t1/2 and AUC values of levodopa. At the same time the urinary excretion of levodopa increased and that of dopac decreased. The plasma ratios of levodopa/dopamine and levodopa/dopac and the urinary ratio of levodopa/dopac also increased. There were less subjective side-effects in the 1:4 groups than in the 1:10 groups. It is concluded that increasing the amount of carbidopa in relation to levodopa may be beneficial and further clinical studies are clearly indicated.