Adenosine 5'triphosphate (ATP) as well as [3H]-noradrenaline ([3H]-NA) is released by perfusion of the vas deferens with the indirect sympathomimetic tyramine (100 microM); this result is consistent with the concept of sympathetic cotransmission. 2. While tyramine produced a strong contraction in the vas deferens of the rat, it had little mechanical action in the guinea-pig vas deferens. This appears to be largely because tyramine induces considerably lower levels of release of both ATP and NA from the guinea-pig vas deferens compared to that of the rat. Furthermore, NA released by tyramine appears to release ATP from a secondary pool in the rat vans deferens, but not that of the guinea-pig, since prazosin reduced the tyramine-induced release of ATP in the rat vas deferens. 3. alpha,beta-Methylene ATP (alpha,beta-meATP) increased both the spontaneous release of ATP and the tyramine-evoked efflux of ATP and [3H]-NA. The basal and tyramine-induced efflux of [3H]-NA was also enhanced by the alpha 1-adrenoceptor antagonist, prazosin, suggesting that prejunctional alpha 1-adrenoceptors may modulate neurotransmitter release.