Previous work has shown that the synthesis and release of dopamine may, under certain conditions, be influenced by an increase in the availability of its amino acid precursor, tyrosine. To examine whether exogenously supplied tyrosine could potentiate the methylphenidate-induced release of dopamine, seven Sprague-Dawley rats were implanted with microdialysis probes aimed at the right nucleus accumbens. Samples were collected from awake, freely moving animals beginning 20-24 hr after surgery. A repeated measures design was used involving the continuous collection of 20-min samples for a 4-hr period, once a day for 3 consecutive days. On a given day, the animal was infused with either 30 uM methylphenidate, 100 uM tyrosine or 30 uM methylphenidate plus 100 uM tyrosine. Periods of infusion with the active compound(s) were preceded and followed by baseline conditions and treatments were counterbalanced to control for possible order effects. Methylphenidate plus tyrosine significantly increased extracellular levels of dopamine in comparison to drug alone. Moreover, this effect was long-lasting, persisting into the post-treatment sampling period and peaking 40 min after the peak induced by methylphenidate alone. Tyrosine alone induced a small but steady rise in extracellular dopamine that did not reach statistical significance until the time of the first post-treatment sample. These findings have implications for the treatment of attention deficit hyperactivity disorder.