The dopamine D4 receptor has lately attracted interest since it has been hypothesized to be involved in the pathogenesis and pharmacotherapy of neuropsychiatric diseases. The present study provides first in vivo evidence of dopamine D4 receptors in primate brain using a [11C]benzo[g]quinoline, the novel radioligand [11C]SDZ GLC 756 ([11C]GLC: in vitro dissociation constants at human receptor clones [nM]: 1.10 at D1; 0.40 at D2; 25 at D3; 0.18 at D4.2; 6.03 at D5). Dynamic positron emission tomography scans were performed on healthy baboons (Papio hamadryas, n = 3). Specific receptor binding (SB) was calculated for striatum and neocortex (frontal, temporal, parietal, and occipital) based on the differences between the regional and the cerebellar concentration of [11C]. Blockade of D1 and D5 receptors by SCH23390 (1.7 pmol/kg) diminished SB in the striatum by 55 +/- 4% (mean +/- standard deviation, P < 0.05) and in the frontal cortex by 13 +/- 8% (P < 0.05) when compared to SB in the unblocked state (SB(D1-D5)). In the presence of the dopamine antagonists SCH23390 (1.7 micromol/kg) and raclopride (5.7 pmol/kg)--which mask the D1, D2, D3, and D5 subtypes--SB of [11C]GLC to D4 receptors (SB(D4)) was demonstrated in the striatum and all cortical regions of interest. In the striatum, the ratio of SB(D4)/SB(D1-D5) was 0.13 +/- 0.07. In the neocortex, SB(D4)/SB(D1-D5) was notably higher (0.77 +/- 0.29; mean of all cortical regions of interest). The widespread distribution of dopamine D4 receptors suggests a basic functional role of this receptor subtype in the modulation of cortical and subcortical neuronal activity.