Evidence that the dopamine transporter is a principal target of cocaine in the brain is supported by the neuroanatomical distribution of cocaine to dopamine-rich brain regions (Volkow et al., 1989, Madras and Kaufman, 1994). Significant levels of cocaine are also detectable in regions of low dopamine transporter density. We investigated the pharmacokinetic properties of [11C] c]ocaine in brain regions of three cynomolgus monkeys administered trace doses of 180-200 MBq of [11C] c]ocaine (N[11C]H3, spec. act. 30-70 GBq/umol). [11C] Cocaine accumulated rapidly in caudate-putamen with peak levels of radioactivity observed within 10-15 min followed by a decline. In cerebellum, peak levels of radioactivity were achieved within 3 min and radioactivity decreased thereafter. In the ventral region of frontal cortex, the pharmacokinetic properties of (C-11)cocaine differed significantly from other brain regions. [11C] Cocaine accumulated within the first two minutes of the imaging session and remained stable for at least 80 min. In contrast to the activity of [11C] c]ocaine in caudate-putamen, unlabeled cocaine (0.6 mg/kg) injected at 20 min did not significantly reduce [11C] c]ocaine accumulation in this region of frontal cortex. This study suggests that a focal region of the frontal cortex binds [11C] c]ocaine or a radioactive metabolite differently from other brain regions. Distribution of [11C] c]ocaine (% of inj. dose/100 ml) 20 min 40 min 60 min 80 min Striatum 15.7 q 2.6 12.3 q 1.8 9.2 q 1.4 7.8 q 1.1 Cerebellum 8.1 q 1.2 5.8 q 0.7 5.0 q 0.6 4.3 q 0.7 Lower lobe of frontal cortex 9.5 q 3.4 9.8 q 3.4 9.8 q 3.3 8.9 q 2.8