We investigated whether muscarinic M(2) receptors, known to inhibit adenylyl cyclase activity in airway smooth muscle, also inhibit isoprenaline-induced relaxation of guinea pig tracheal smooth muscle, as has recently been described for the dog (Fernandes et al., 1992, J. Pharmacol. Exp. Ther. 262, 119). Smooth muscle strips were contracted with various concentrations of methacholine or histamine (which served as a control) in the absence or presence of the M(2)-selective muscarinic receptor antagonist, gallamine (30 mu M), and cumulative isoprenaline-relaxation curves were obtained. It was found that muscarinic M(2) receptor blockade had no significant effect on isoprenaline pD(2) and E(max) values, neither with histamine nor with methacholine. The results show that, in guinea pig trachea, muscarinic M(2) receptors do not significantly influence the functional antagonism of cholinergic smooth muscle contraction by isoprenaline.