Primary cultures of cerebellar neurons obtained from 7-9-day-old rats and grown 7-9 days in vitro @IV) were used to study the effects of Na+ and Ca++ on K + -evoked taurine release. These cultures, made up largely of granule neurons (90%) and inhibitory interneurons (5-7%), produced a dose-dependent, depolarization-evoked taurine release that was Ca+ + - dependent at 40 mM K+, and Ca++-independent at K+ concentrations above 40 mM. The dihydropyridine Ca++ channel agonist BAY K 8644 (1 pM) augmented 30 mM K+-evoked release, while the antagonist nifedipine (5 pM) abolished both the BAY K 8644and K+-enhanced release. Depolarization with the Na+ channel agonist veratridine (50 p M ) stimulated taurine efflux, which was completely blocked by pretreatment with tetrodotoxin (2 p M ) . However, 50 mM K+-evoked taurine release was not affected by tetrodotoxin pretreatment. Substitution of choline C1 for NaCl partially antagonized 50 mM Kfevoked release, and by itself, the Na+ ionophore monensin (50 p M ) stimulated release. These results suggest that both K+-evoked and basal taurine release from primary cerebellar neuronal cultures are sensitive to the levels of both intracellular and extracellular Na+ and Ca++. In contrast to previous findings using cerebellar astrocytes, neuronal L-type Ca+ + channels, but not voltage-dependent Na+ channels, also appear to be necessary. The implications of these results on taurine's status as a putative neurotransmitter are discussed.