Primiphos-methyl and methidathion as organophosphorus (OP) pesticides were tested for their immunotoxic effects on Balb/c mice. Three dose levels of primiphos-methyl (10, 60, or 120 mg/kg/day) and methidathion (0.5, 2.5 or 5.0 mg/kg/day) were administered orally in the mice for 4 weeks. After, changes in body weight gain, relative weight of spleen and thymus, viable splenic cell numbers, surface marker on immune cell, and proliferation activity were investigated. Results showed that neither Pirimiphos-methyl nor methidathion dosages changed significantly body weight, relative thymus and spleen weight, and thymus and spleen cellularities of the mice, but high dose treatment (120 mg/kg) of pirimiphos-methyl significantly decreased relative spleen weight and spleen cellularity of the mice. No alterations were observed in changes of LPS-proliferation response of splenocytes by exposure to any dose of pirimiphos-methyl and methidathion. However, pirimiphos-methyl dosages reduced ConA-proliferation response of splenocytes and both methidathion and pirimiphos-methyl decreased the ability of antibody production to SRBC. The results indicate that 28 days exposure to the high dose of pirimiphos-methyl suppress the function of splenic T and B cell function, and methidathion reduce the immune responsibility of B cell in mice without the changes in lymphoid organ weight or viability of splenocytes. Pirimiphos-methyl is more immunotoxic than methidathion although this has higher general toxicity than that.