By microdialysis in the unilateral caudal ventrolateral medulla (CVLM) of anesthetized rats, the spontaneoUS L-3,4-dihydroxyphenylalanine (L-DOPA) release was in part tetrodotoxin-sensitive or Ca2+-dependent and was abolished by i.p. alpha-methyl-p-tyrosine (alpha-MPT), a tyrosine hydroxylase inhibitor. High K+ (50 mM) Ca2+-dependently evoked L-DOPA. By unilateral microinjections into the CVLM, L-DOPA (10-100 ng) produced dose-dependent, marked hypotension and bradycardia similarly in rats untreated, treated with i.p. 3-hydroxybenzylhydrazine, a central DOPA decarboxylase inhibitor, or with i.v.t. 6-hydroxydopamine. These responses were antagonized by L-DOPA methyl ester, a competitive L-DOPA antagonist. A depressor response to dopamine or noradrenaline (100 ng) was far smaller and slower in onset than that to L-DOPA (30 ng). D-DOPA (100 ng) produced no effect. Furthermore, L-DOPA methyl ester microinjected into bilateral CVLM produced some hypertension and tachycardia, which were markedly reduced by alpha-MPT. Transmitter-like L-DOPA tonically functions to mediate vasodepressor control in CVLM of rats.