Abstract Possible modulatory effects of histamine (HA) on electrically-evoked neurotransmitter release from slices of a number of rat brain regions were investigated. Neither the release of [ 3H]DA nor that of [ 14C]ACh from neostriatal slices were affected by HA (up to 3 μM). In contrast, HA (1 μM) inhibited the release of [ 3H]NA from slices of both frontal cortex and hypothalamus by 25% and 37%, respectively. The strongest inhibitory effects of HA (40–50% at 1 μM) were found with regard to [ 3H]5-HT release from slices of all three brain regions examined. In the frontal cortex [ 3H]5-HT release was inhibited by HA with an EC 50 of about 0.1 μM and further pharmacological experiments suggested that the receptors involved in this inhibitory effect are of the H 3 type. Also in view of data reported by others it is suggested tentatively that in general presynaptic modulation of neurotransmitter release by histamine, if it occurs, involves activation of H 3 receptors.