Topical citrate has been shown to significantly reduce the severity and incidence of corneal ulceration in alkali-burned rabbit eyes. Subcutaneous injection of citrate significantly reduced the severity of ulceration. This study was performed to determine the plasma citrate and ionized calcium levels after systemic administration of citrate. Repeated ingestion of citric acid capsules showed a small increase in the plasma citrate level, but no significant change in the level of ionized serum calcium 30 min after the last ingestion. A single dose of Polycitra-LC (6.672 g of citrate) more than doubled the baseline citrate concentration but only induced a 5% decrease in the level of ionized serum calcium 30 min after ingestion. Neither regimen of orally administered citrate produced any significant effect on the respiratory burst or adherence of in vitro polymorphonuclear leukocytes (PMNs) resuspended in their respective plasma. In comparison studies, higher levels of plasma citrate and lower levels of ionized serum calcium were achieved through plateletpheresis. The respiratory burst and adherence of PMNs were not statistically different from baseline PMNs. However, there was an inverse correlation between the micromolar increase in citrate or the micromolar decrease in calcium and the respiratory burst. These results suggest that the use of oral citrate alone may not be practical, but does not preclude the use of oral citrate as a supplement to topical citrate.