The immune and hematological systems can be a target for environmental contaminants with potential adverse effects, so the purpose of this study is to provide documentation on immunotoxicity and hematotoxicity of tetrachloroethylene, which is widely used in dry cleaning in Egypt. This study was carried out on 80 adult males. Subjects designated as controls (n = 40) were healthy persons and others were tetrachloroethylene-exposed dry-cleaning workers (n = 40). The controls and tetrachloroethylene-exposed workers were then divided into four equal groups (20 individuals/group): group I, control group never smoking; group II, smoking control group; and groups III and IV, tetrachloroethylene-exposed nonsmoking and smoking workers, respectively. Blood level of tetrachloroethylene, complete blood count, immunoglobulins (IgA, IgM, IgG, and IgE), the total numbers of white blood cells (WBC), and leukocyte differential counts, as well as interferon gamma (IFN-gamma) and interleukin-4 (IL-4), were measured. The immunotoxicity of tetrachloroethylene appeared in the form of an increase in serum immunoglobulin E in nonsmoking and smoking tetrachloroethylene-exposed workers, while the serum immunoglobulins A, M, and G levels showed no significant change in all studied groups. In addition, our results demonstrated a significant increase in white cell count, lymphocytes, natural killer (NK; CD3+CD16CD56+) cells, and B (CD19+) lymphocytes. The increase in WBC and lymphocytes may be attributed to allergic reaction. Moreover, serum and lymphocytic interlukin-4 levels were significantly increased in nonsmoking and smoking tetrachloroethylene-exposed workers. Tetrachloroethylene exposure is associated with immunotoxicity, which may lead to the augmentation of allergic diseases or appearance of autoimmune reaction.