Standard two electrode voltage clamp techniques were used to investigate the response of neuronal nicotinic acetylcholine receptors, expressed in Xenopus oocytes, to various agonists and neuronal bungarotoxin (NBT). The beta subunit is an important determinant of the receptor's pharmacological profile. Co-expression of alpha 4 and beta 2 subunits produced a receptor that was relatively insensitive to cytisine and nicotine and inhibited by NBT, whilst the alpha 4 beta 4 combination produced a receptor that was highly sensitive to cytisine and nicotine but resistant to toxin. The first 80 amino acids of the N-terminal domain of the beta subunit are implicated in these characteristics, since the combination of alpha 4 with a hybrid beta subunit comprising amino acids 1-->80 of beta 2 and 81-->416 of beta 4 became relatively insensitive to nicotine and cytisine and resistant to inhibition by neuronal bungarotoxin.