In vitro incubation of adrenaline with acetaldehyde resulted in the formation of an amorphous product (MA 3) which gave origin to two spots on chromatography plates. Preparative TLC allowed us to separate the corresponding substances, MA 4 and MA 5. Gas chromatography-mass spectrometry, ultraviolet and infrared spectra of MA 4 agree with the structure corresponding to 1,2-dimethyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline. MA 5 is very unstable and was not further characterized. Pharmacological experiments were carried out with MA 3 and MA 4 (and in some cases, MA 5) on isolated saphenous vein strips and isolated guinea-pig atria; responses of the nictitating membrane, blood pressure and hind-limb perfusion pressure were obtained in the anaesthetized dog. There were only quantitative differences between the effects of MA 3, MA 4 and MA 5 (where tested). Therefore, these effects are described as effects of TIQs (tetrahydroisoquinolines). TIQs contracted isolated saphenous vein strips, behaving as total agonists; the dose-response curves were displaced to the right by phentolamine and to the left by cocaine (potentiation factor: 2.7 +/- 0.1). In the dog, contractions of the nictitating membrane, rises of blood pressure and of the perfusion pressure (after i.a. injection) were observed. On isolated guinea-pig atria, weak beta adrenergic receptor activation was found. With higher concentrations, beta receptor blockade was observed, for both cardiac and vascular smooth muscle receptors. The effects of TIQs were short-lasting, showing that a rapid inactivation occured both in vitro and in vivo; neuronal uptake appears to play an important role in inactivation, since cocaine was able to block about 70% of the inactivation capacity of isolated vein strips. The effects of nerve stimulation on the vein strips or on the nictitating membrane were reduced by TIQs; however, this did not affect responses to noradrenaline and enhanced those to tyramine or DMPP. Simultaneously with reduction of the effects of electrical stimulation, blockade of inactivation of endogenous and exogenous noradrenaline was induced by TIQs. Marked depletion of noradrenaline levels in the heart, hypothalamus and aorta of the guinea pig was caused by MA 3 (1-3 mg/kg). It is concluded that the condensation products of adrenaline with acetaldehyde are not devoid of pharmacological activity, are taken up by adrenergic nerve terminals and may act as false transmitters. The similarity of effects of TIQs and acetaldehyde suggests that formation of TIQs may occur in vivo, after acetaldehyde (or ethanol) administration, both in the adrenal gland and in sympathetic nerve terminals. These TIQ alkaloids could play an important role in alcoholic intoxication and in the ethanol withdrawal syndrome.