The longitudinal muscle of the guinea pig ileum is well known to contract in response to stimulation of either muscarinic or histamine H1 receptors. However, we found that simultaneous application of agonists to both receptors, methacholine (MeCh) and histamine (Hist), at their maximum concentrations (both at 10(-5) M), induced a contraction of the muscle with a pattern very similar to that observed with MeCh alone. In the muscle contracted by MeCh, a muscarinic antagonist, atropine, caused a transient relaxation, but a histamine H1 blocker, pyrilamine, had no effect on the tension. Experiments using pirenzepine indicated that muscarinic-M1 receptors did not seem to be involved in the mechanism of this phenomenon. The atropine-induced relaxation was not affected by phentolamine (10(-6) M), propranolol (10(-6) M) or tetrodotoxin (10(-6) M). After pretreatment of the muscle with 10(-5) M MeCh for 10 min, the contractile effect of 10(-5) M Hist was suppressed intensely for a certain time period, but that of 10(-5) M MeCh was not diminished. On the other hand, pretreatment of the muscle with 10(-5) M Hist for 10 min did not influence the contraction by either MeCh or Hist. The suppression by MeCh of the Hist action developed dependently on the concentration of MeCh and the time length of exposure to MeCh, and the persistence was temperature-dependent. Furthermore, this suppression was not surmounted by the elevation of Hist concentration. A similar phenomenon was also observed in the muscle which was immersed in the nutrient solution without CaCl2.(ABSTRACT TRUNCATED AT 250 WORDS)