We examined the effects of lithium treatment on the synthesis and secretion of catecholamines in cultured bovine adrenal medullary cells. The treatment of cells with lithium (0.5-4 mmol/L) for 7 days caused an increase in basal and carbachol-stimulated synthesis of 14C-catecholamines from [14C]-tyrosine but not from [14C]-DOPA. Lithium treatment (4 mmol/L, 7 days) increased the activity of tyrosine hydroxylase in the cells. Lithium treatment (2-4 mmol/L, 7 days) also enhanced the secretion of catecholamines caused by carbachol, although the carbachol-induced influx of 45Ca2+ was reduced. Lithium (4 mmol/L, 7 days) potentiated the secretion of catecholamines evoked by the Ca2+ (1 mumol/L) from cells that were permeabilized by digitonin. The activity of protein kinase C in a soluble fraction was increased in lithium-treated cells (4 mmol/L, 7 days). These results demonstrate that lithium treatment increases the synthesis and secretion of catecholamines and the activity of protein kinase C in cultured adrenal medullary cells.