Tick control strategies rely heavily on chemicals (acaricides), most of which target the central nervous system. With increasing resistance, new acaricides are urgently needed but knowledge of tick neurobiology is surprisingly limited, notably the number of neural-specific gene sequences. One thousand and eight expressed sequence tags (ESTs) were obtained from a normalized cDNA library from Rhipicephalus sanguineus synganglia. Putative functional identities were assigned to 44% whereas 34% were unknown/novel sequences. Of particular interest were ESTs encoding a chitinase-like enzyme, an acetylcholinesterase and four transmembrane receptors including two glutamate-gated chloride channel receptors, a leucokinin-like receptor and a nicotinic acetylcholine receptor alpha-subunit. This study highlights the benefits of using both neural tissues and normalized libraries in an EST-approach for identifying potential acaricide targets expressed as rare transcripts.