After training under a fixed-interval 60 sec schedule of food presentation in the presence of a water tube (to permit schedule-induced licking), groups of rats received either 6-hydroxy-dopamine (6-OHDA)(8 micrograms base/2 microliters) or 0.2% ascorbate-0.9% saline vehicle bilaterally into the nucleus accumbens. 6-OHDA produced greater than 80% depletion of the catecholamines dopamine and norepinephrine and the dopamine metabolite dihydroxyphenylacetic acid in the nucleus accumbens and olfactory tubercle, but nonsignificant depletions in the corpus striatum. The behavior of the groups treated with 6-OHDA ("lesion") and vehicle ("sham") was assessed for up to 58 days postoperatively. In the first few days after 6-OHDA, the lesion group showed reductions in high rates of responding toward the end and in high rates of licking at the beginning of the fixed-interval. However, licking was increased during later portions of the fixed interval in the lesion group. d-Amphetamine (0.25-2.0 mg/kg) increased low rates but decreased high rates of schedule-controlled responding, while generally reducing licking. The lesion group showed attenuated rate-reducing effects of d-amphetamine. In contrast, the lesion group showed enhanced rate-reducing effects of apomorphine (0.025-0.1 mg/kg) on both schedule-controlled responding and schedule-induced licking. In a second determination of the effect of d-amphetamine (0.25-2.0 mg/kg), schedule-induced locomotor activity was recorded and the water tube was removed. The lesion group showed attenuated rate-increasing and rate-decreasing effects of d-amphetamine upon schedule-controlled responding and reductions in the drug-induced increases in locomotor activity. The results are discussed in terms of the functions of dopamine in the control of behavior and in the mediation of the response to d-amphetamine and apomorphine.