This was a randomized, controlled, double-blind trial of zinc sulfate in the treatment of Behcet's disease. Patients with Behcet's disease were recruited in this study between November 2001 and February 2003. A clinical manifestations index (CMI) was calculated for each patient. Serum zinc was estimated in all patients both at the beginning and monthly throughout the trial. Serum zinc levels were estimated from 30 healthy normal subjects matched for age and sex as a control group. Patients were randomly allocated to receive either 100 mg zinc sulfate or identical placebo tablet three times daily in a double-blind manner. After 3 months of starting treatment, patients were crossed over, that is, patients on placebo received zinc sulfate and vice versa. Mean serum zinc level in Behcet's disease patients was statistically significantly lower than mean serum zinc levels in healthy the control. In group A (started with zinc sulfate), the mean CMI started to decline directly after the first month of therapy with zinc sulfate to significantly lower levels. After shifting to placebo treatment in the fourth month, the mean of CMI started to rise again gradually but remained significantly lower than levels before therapy for the fourth and fifth months. In group B (started with placebo), the mean of CMI remained high for the first 3 months. After crossing over to zinc sulfate in the fourth month, the mean of CMI started to decrease after the fourth month. An inverse correlation between CMI and serum zinc level was found. No side-effects were seen in either group. In conclusion, zinc sulfate was found to be a good option in the treatment of Behcet's disease.