To examine whether chronic administration of L-dopa can affect its own utilization in striatum, rats were injected once daily for 30 days with L-dopa and carbidopa or with saline. On day 31, saline and L-dopa animals were sacrificed 1, 2, or 3 hours after L-dopa injection. In rats given long-term L-dopa, the elevations in striatal dopamine concentrations induced by L-dopa administration were smaller and of shorter duration than those in controls. Such changes did not occur in animals pretreated with L-dopa for only 10 days. Results suggest that prolonged L-dopa therapy may decrease striatal accumulation of dopamine from exogenous L-dopa even when the nigrostriatal projections are intact. Therefore, it is possible that declining efficacy of L-dopa in parkinsonism may be due to effects of the drug itself and not only to disease progression.