The effects of the combined exposure of cypermethrin (CY), NaAsO2 (As), and HgCl2 (Hg) were investigated in male Wistar rats following 4 weeks of oral exposure. Standard toxicological (body weight gain, organ weights of brain, thymus, heart, lung, liver. kidneys, adrenals, testes, and popliteal lymph node), haematological (white blood cell, red blood cell, haematocrit. MCV-mean volume of red blood cells. and cell content of the femoral bone marrow), and immune function (IgM-PFC response, delayed type hypersensitivity (DTH) reaction) parameters were measured. The two doses selected for the combination were: a high (H) dose equal to lowest observed effect level determined in preliminary experiments (CY(H) = 55.4 mg/kg, As(H) = 13.3 mg/kg, Hg(H) = 3.20 mg/kg), and a low (L) dose which was ineffective (non-observed effect level); CY(L) = 11.1 mg/kg, As(L) = 3.33 mg/kg, Hg(L) = 0.40 mg/kg). CY(H) was combined with As(L) or Hg(L), and the H doses of the heavy metals were combined with CY(L). Beside vehicle control, the H dose components of the combinations were also used as internal controls. The main finding of this study was that certain combinations, when compared to H dose internal control, significantly altered the body weight gain (As(H) + CY(L)), the relative weight of adrenals and popliteal lymph node (CY(H) + As(L) and CY(H) + Hg(L)), the cell content of the femoral bone marrow (CY(H) + Hg(L)), and the time course of DTH reaction (CY(H) + As(L)). According to the present results, combined exposure with CY and the heavy metals investigated can modify the toxicity and/or the functional detection limit of the single substances. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.