Information on the fetal brain in Down syndrome (DS) is limited. In particular, there is no systematic study available on cholinergic, monoaminergic or serotoninergic innervation in the early second trimester. It was therefore the aim of the study to investigate whether deficits of any of these systems known to occur in adults with DS, was present at this early phase. For this purpose we determined markers for neuronal density (neuron-specific enolase, NSE), for cholinergic innervation (vesicular acetylcholine transporter, VAChT), for monoaminergic innervation (vesicular monoamine transporter 2, VMAT2; tyrosine hydroxylase, TH) and for the serotoninergic system (serotonine transporter, SERT) in brain of control and DS fetuses in the early second trimester using immunoblotting. Values for all neurotransmission systems were measurable at this time point of human development and comparable in control and DS fetuses. We conclude that during the second trimester DS patients do not differ in terms of immunoreactivity for all markers studied. This first study on that subject warrants further investigations for the determination of the time point when neurotransmitter deficits in DS brain are starting, a hallmark most important for pathogenesis and pharmacotherapy.