Binding activities specific for each of [ 3H]prostaglandin (PG) D 2, E 2 and F 2α were detected in the P 2 fraction of the human brain homogenates. The bindings were time-dependent, saturable and of high affinity; K dvalues were 30 nM for all the PG bindings. Regional distribution of these binding activities was determined by measuring specific bindings with 10 nM [ 3H]PG-D 2, [ 3H]PG-E 2 and [ 3H]PG-F 2α in the P 2 fractions from 17 brain regions. The PG-D 2 binding activity was high in the hypothalamus, amygdala and hippocampus followed by cerebellar nuclei, thalamus, nucleus accumbens and cerebral cortex. The PG-E 2 binding sites were similarly concentrated in the hypothalamus and the limbic system, but, unlike the PG-D 2 binding, no significant binding of [ 3H]PG-3 2 was observed in cerebellar nuclei, cerebellar cortex and putamen. Compared with these two PG bindings, PG-F 2α binding activity was low in many areas, but significant binding was detected in the amygdala, cingulate cortex, cerebellar medulla, hippocampus, nucleus accumbens, midbrain and hypothalamus. These results suggest the presence and specific distribution of three distinct types of PG binding activities, i.e. specific binding of PG-D 2, PG-E 2 and PG-F 2α, in the human brain.