Exposure of bovine chromaffin cells in primary culture to 0.01-1 microM reserpine caused a dose- and time-dependent increase in intracellular levels of the amidated enkephalin peptide metorphamide. Maximal levels (approximately 800% of control) were obtained at 0.1 microM reserpine and increased levels were apparent by 16 h of treatment. Metorphamide increases were at least fivefold more than that of either Met- or Leu-enkephalin, suggesting that reserpine stimulates both enkephalin processing and amidation in the secretory vesicle. Treatment with elevated potassium, which increases enkephalin levels by stimulating production of preproenkephalin messenger RNA, elicited an increase in metorphamide levels equivalent to, but not greater than, the increase in Met-enkephalin pentapeptide. The ratio of Met-enkephalin to metorphamide in untreated chromaffin cells is approximately 140:1, whereas the final Met-enkephalin: metorphamide ratio in reserpinized chromaffin cells is approximately 30:1, similar to the Met-enkephalin:metorphamide ratio in enkephalinergic neurons of the CNS.