Results of recent studies suggest that dopamine (DA) transmission in the caudate-putamen may be involved in food reward-related learning. The purpose of the present study was to evaluate this hypothesis by injecting the DA antagonist cis-flupenthixol (25 micrograms in 0.5 microliters) into the dorsal caudate-putamen of rats (n = 19) trained to lever press for food presented according to a variable interval 30-s schedule. Additional groups received non-reward (n = 8), systemic cis-flupenthixol (0.01, 0.1 mg/kg i.p.; ns = 8), dorsal caudate-putamen injections of the inactive isomer trans-flupenthixol (n = 10), frontal cortical (dorsal to the caudate-putamen site) injections of cis-flupenthixol (n = 6), or cis- or trans-flupenthixol injected into the nucleus accumbens (ns = 9, 8) or amygdala (ns = 6, 5). Rats were tested in 30-min sessions and response rates were recorded every 5 min. As expected, non-reward produced a gradual decline in responding. A similar pattern was seen in the groups receiving systemic (0.1 mg/kg) or dorsal caudate-putamen injections of cis-flupenthixol. No significant effect was seen following systemic (0.01 mg/kg), cortical or amygdala cis-flupenthixol or dorsal caudate-putamen or amygdala trans-flupenthixol. Accumbens cis-flupenthixol reduced rates but did not produce a gradual decline in responding; however, accumbens trans-flupenthixol led to a time-dependent elevation in response rates making interpretation of the accumbens results difficult. It was concluded that dopaminergic projections to the dorsal caudate-putamen may play a critical role in mediating the effects of food-reward on operant responding.