The effect of diabetes-induced chronic tyrosine (Tyr) deficiency on dopamine (DA) synthesis in different areas of the mesotelencephalic DA system was examined. Diabetes was induced using streptozotocin. In vivo Tyr hydroxylation was used as an index of DA synthesis. The brain areas examined were prefrontal cortex (PFC), pyriform cortex (PYR), olfactory tubercle (OT), caudate-putamen (CP), substantia nigra (SN), and ventral tegmental area (VTA). Significant decreases in Tyr hydroxylation were observed in PFC, CP, and PYR. The largest decrease was seen in the PFC. Variations in tissue Tyr levels were shown to account for 62% of the variability in Tyr hydroxylation in the PFC, and 23% of the variability in the CP; a significant correlation between Tyr levels and Tyr hydroxylation was not seen in the other brain areas. The mechanisms underlying this regionally selective effect, and possible clinical relevance are discussed.