The study examined the effect of levamisole on the natural cytotoxic cell (NCC) activity of Nile tilapia (Oreochromis niloticus) head kidney (HK) leukocytes. In vitro, HK leukocytes were incubated with $10^{-4}$ to $10^4$ ng of levamisole/ml for 5, 20 or 40 h and then their NCC activity against target cells was assayed. The NCC activity appeared to increase after a 20 h of incubation. In vivo, tilapia were fed commercial diet containing 0, 50, 100 or 300 mg of levamisole/kg for 12 consecutive days. Then, the fish were fed a commercial normal diet and samples harvested weekly 0 to 8 weeks after levamisole administration. The NCC activity was augmented uniformly at all times examined until the end of the experiment. In conclusion, levamisole effectively enhanced and maintained tilapia NCC activity.