Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li + interactions in red blood cells (RBCs) have been identified. We investigated Li + interactions on human neuroblastoma SH‐SY5Y cells by developing a novel 7 Li NMR method that provided a clear estimation of the intra‐ and extracellular amounts of Li + in the presence of the shift reagent thulium‐1,4,7,10‐tetrazacyclododecane‐ N,N ′, N ″, N ‴‐tetramethylene phosphonate (HTmDOTP 4− ). The first‐order rate constants of Li + influx and efflux for perfused, agarose‐embedded SH‐SY5Y cells in the presence of 3 m M HTmDOTP 4− were 0.055 ± 0.006 (n = 4) and −0.025 ± 0.006 min −1 (n = 3), respectively. Significant increases in the rate constants of Li + influx and efflux in the presence of 0.05 m M veratridine indicated the presence of Na + channel‐mediated Li + transport in SH‐SY5Y cells. 7 Li NMR relaxation measurements showed that Li + is immobilized more in human neuroblastoma SH‐SY5Y cells than in human RBCs.