We have studied the effect of L-ascorbic acid (vitamin C) on copper metabolism using copper-deficient chicks and the activation of lysyl oxidase copper-dependent enzyme, to assess bioavailability of copper. When administered intraperitoneally with (or 75 minutes before) CuSO4, L-ascorbate significantly impared the effectiveness of copper to restore lysyl oxidase activity in deficient chicks. L-ascorbate given 75 minutes after CuSO4 (i.e., in the post-absorption period), however, produced a substantial increase in copper-induced enzyme activation. L-ascorbate by itself showed no direct stimulating effect in deficient chicks. When the L-ascorbate was given to chicks that had received adequate dietary copper, there was a strong rise in ceruloplasmin and a slight, but significant increase in lysyl oxidase. An increase in ceruloplasmin in response to copper was also seen in deficient chicks and L-ascorbate also augmented that increase. Substituting D-isoascorbic acid for antagonistic properties of L-ascorbic acid on copper metabolism, but they also reveal possible sterospecific postabsorption roles for L-ascorbate in the metabolism of copper.