The influence of endogenous nitric oxide (NO) on neuroeffector transmission in segments of guinea pig pulmonary artery was analyzed by application of NG-monomethyl-L-arginine (L-NMMA). L-NMMA enhanced contractile responses to nerve stimulation and this enhancement was counteracted by L-arginine. The enhancement remained after removal of the endothelium. L-NMMA enhanced contractions to exogenous noradrenaline. After blockade of adrenergic transmission by phentolamine, L-NMMA enhanced contractions induced by nonadrenergic-noncholinergic (NANC) neurotransmission. Stimulation-induced release of [3H]noradrenaline was unchanged by L-NMMA. The results suggest that endogenous NO exerts a postjunctional inhibition on adrenergic neurotransmission in the guinea pig pulmonary artery. A concomitant pre- and/or postjunctional inhibition of NANC transmission is implicated. The neuromodulation by NO does not require an intact endothelium.