Neurotransmitter-specific anatomical techniques have provided a tool to define the morphological constraints within which a given neurotransmitter will exert its cellular actions. Biochemical and electrophysiological approaches have revealed the nature of these cellular actions for several neurotransmitters. Furthermore, by using purified preparations and tissue cultures a certain degree of resolution has been achieved by which the cell type, where a neurotransmitter's effect takes place, can be determined. In this article we review these aspects for noradrenaline and vasoactive intestinal peptide, two neurotransmitters of the cerebral cortex contained within neuronal systems that present strikingly different morphologies. Nevertheless, noradrenaline and vasoactive intestinal peptide share certain cellular actions and can interact synergistically. The experimental evidence accumulated to date indicates that noradrenaline- and vasoactive intestinal peptide-containing neurons can influence three general cell types of the cerebral cortex, i.e. (i) other neurons, (ii) astrocytes and (iii) cells of the vasculature. This diversity in cellular partners supports the notion that noradrenaline and vasoactive intestinal peptide can be released from neurons at conventional synapses as well as at extrasynaptic sites, thus suggesting the co-existence of two modes of release within the same neuron.