Standard two-electrode voltage-clamp techniques were used to investigate some of the pharmacological and functional properties of two types of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes after pairwise injection of alpha 3 beta 4 or alpha 3 beta 2 mRNAs. Currents of several microA amplitude were elicited by fast application of micromolar concentrations of either acetylcholine (ACh) or 1,1-dimethyl-4-piperazine (DMPP). The activation of either receptor type by DMPP showed cooperativity (Hill coefficient, n greater than or equal to 1.7) with a half-maximal activation concentration (EC50) of 15-30 microM. In alpha 3 beta 4 receptors, ACh displayed cooperativity (n = 1.8) but was less efficacious than DMPP, yet its EC50 was about equal to that of DMPP. Finally, in alpha 3 beta 2 receptors, ACh was much less efficacious and had a much lower EC50. Desensitization induced by either DMPP or ACh was slow in alpha 3 beta 4 nicotinic ACh receptors but was rapid and extensive in alpha 3 beta 2 receptors, causing a significant proportion of the response to wane within the first few seconds of agonist application.