Effects of combined exposure with dimethoate (DM), HgCl2 (Hg), and NaAsO2 (As) were investigated following a 28-day oral exposure in male Wistar rats. In preliminary experiments, the LOEL (Lowest Observed Effect Level) and NOEL (Non Observed Effect Level) doses of the substances were determined using the same experimental system [determination of body weight gain, organ weights of brain, thymus, heart, lung, kidneys, adrenals, spleen, testicles, popliteal lymph node, white blood cell (WBC) and red blood cell (RBC) count, haernatocrit (Ht), mean cell volume (MCV) of RBCs, cell content of the femoral bone marrow, IgM-plaque forming cell (PFC) content of the spleen, delayed type hypersensitivity (DTH) reaction] and animal strain. In the combination studies, LOEL dose of DM (28.2 mg/kg) was combined with NOEL doses of the heavy metals (HgCl2 = 0.40 mg/kg, NaAsO2 = 3.33 mg/kg), and vice versa (DM = 7.04 mg/kg, HgCl2 = 3.20 mg/kg, NaAsO2 = 13.3 mg/kg). In the DM-Hg combinations, significant alterations were found versus the corresponding high-dose internal control in the body weight gain, relative liver and kidney weights, and in the PFC response. When DM was combined with As, interactions were indicated by changes of relative liver weight, MCV value, and the PFC content of the spleen.