The ability of derivatives of 2-aminotetralins (2AT), cis- or trans-isomers of octahydrobenzo[f]quinolines (BfQ) and clonidine to modulate acetylcholine release was studied using field-stimulated guinea pig ilea (GPI). Antihistaminic and antiacetylcholine activities were also determined using isolated superfused segments of GPI. Hydroxylated 2AT, BfQ and clonidine inhibited field stimulation-induced contractions through α-adrenoceptor mechanisms which were antagonized by phentolamine. In contrast, the inhibition produced by nonhydroxylated 2AT was not attenuated by α-adrenoceptor antagonism. 2AT, trans-7,8-dihydro-BfQ and cis-8,9-dihydroxy-BfQ inhibited contractions induced by nicotine bitartrate using superfused GPI. Clonidine was inactive as an antinicotinic agent and there was no correlation between a compound's ability to inhibit contractions induced by field stimulation and its antinicotinic activity. Various 2AT derivatives demonstrated weak antimuscarinic and/or antihistaminic activities on superfused ileal segments. These data demonstrate that these agents posses a spectrum of pharmacological activity.