Sir,I read with great interest the article by Bajait and Thawani.[1] The authors have reviewed the available evidence on the efficacy and safety of zinc supplementation in pediatric diarrhea and convincingly concluded that, zinc supplementation has a beneficial impact on the disease outcome. Although the authors have nicely reviewed the recommendation, following points in the paper need comment. The authors have described that, the physiological effect of zinc on intestinal ion transport has not yet been established thoroughly and a very recent publication has shown zinc not to inhibit Ca2+ mediated potassium K+ channels. However, this is not entirely true. Some recent reports instead have shown that, effect of zinc in acute diarrhea may vary according to the etiological agents. One study showed that, zinc is able to inhibit all (cAMP, nitric oxide, Ca2+) except the cGMP-mediated intracellular pathways of intestinal ion secretion.[2] Actually, rotavirus, the major agent of acute diarrhea in infancy, stimulates Cl- secretion through a phospholipase C-dependent Ca2+ signaling pathway and zinc has been shown to be effective in acute diarrhea caused by this organism. On the other hand, zinc might not be effective in the treatment of acute diarrhea caused by organisms that act through the cGMP pathway, even in the developing country. Another study found the effect of zinc in acute diarrhea according to the etiological agents as follows - being beneficial in acute diarrhea caused by Klebsiella, neutral in Esherichia coli and parasitic infections, and more importantly zinc was detrimental in diarrhea caused by rotavirus infections.[3]The authors also described that, zinc is probably effective in acute diarrhea even in the absence of zinc deficiency. This might not also be true, as a recent randomized clinical trial (RCT) in Polish children did not show any benefit, and the authors concluded that, children living in a country where zinc deficiency is rare do not appear to benefit from the use of zinc in the treatment of acute gastroenteritis.[4] Similarly, in another RCT conducted in well-nourished Turkish children, zinc therapy did not change either the duration or severity of the diarrhea.[5] The explanations for this differential effect of zinc helping only children from developing countries might be due to the fact that, zinc deficiency (secondary to malnutrition, diarrheal disease itself causing excess zinc loss in stool, dietary factors causing decreased absorption of zinc, decreased intake due to poor socio-economic status, etc) is associated with impaired water and electrolyte absorption, decreased brush-border enzymes and impaired cellular and humoral immunity, commonly in these populations rather than in children from developed countries.To conclude, understanding of above factors including the role of etiological agents in zinc and acute diarrhea trials would identify children most likely to benefit from therapeutic zinc supplementation.