The ability of 2-aminotetralins (2-ATs), 2-aminoindanes (2-AIs), morphine (M) and clonidine (CLON) to alter neuroeffector transmission was studied on field-stimulated (FS) guinea-pig ilea (GPI). The activity of these compounds to inhibit K+, histamine (H), actylcholine (ACh), nicotine (Nic) and serotonin (5-HT) induced contractions was determined using superfused GPI segments. 2-ATs, 2-AIs, M and CLON dose-dependently inhibited contractions produced by low frequency stimulation through alpha-adrenergic, opioid or unknown receptor mediated mechanisms. 2-ATs inhibited ACh, Nic, 5-HT and FS, but not K+- or H-induced contractions. 2-ATs, 2-Ais and M were more potent than hexamethonium in inhibiting Nic-induced contractures. 2-AT and 2-AI-induced inhibition was not antagonized by naloxone or phentolamine. However, the inhibitory effects of 2-ATs. 2-AIs and M on FS-GPI were antagonized by increasing the concentration of Ca2+ ion in the media. These data are consistent with the supposition that 2-ATs, 2-AIs or M alter neuroeffector transmission through competitive changes in Ca2+ disposition in cholinergic neurons of guinea-pig isolated ilea. A discussion relating other biological actions of 2-ATs or 2-AIs (e.g. alpha-adrenergic mediated antinociception) to the observed inhibitory neuroeffector responses is provided.