The present study was carried out to help elucidate the possible mechanisms underlying the effect of Cd and the interaction of Se with Cd on blood pressure. Male Wistar rats were divided into four groups: control, Cd-treated, Se-treated, Se-and Cd-treated. Cd and Se were administered at doses of 1.0 mg/kg body weight by subcutaneous injection of aqueous solutions of CdCl2·2×1/2 H2O and Na2SeO3, respectively. Injections were made either alone or in the Cd+Se treated group, simultaneously at 12−h intervals for 7 consecutive days. All animals were then maintained without further treatment for an additional period of 18 days. Treatment with Cd and Se separately lowered the blood pressure on days 3 and 8, but these levels increased and were significantly higher than that in control rats by day 26. Plasma aldosterone concentrations increased and urinary Na excretion decreased from day 1 to 3 in rats treated with Cd and Se separately. Thereafter, increased water retention precedes the onset of increased blood pressure. From these findings, we suggest that in rats treated with Cd and Se separately the increase in plasma aldosterone is a main factor for decreased urinary Na excretion and increased retention of water, and these factors may be associated with an increase in blood pressure. The treatment with Cd and Se simultaneously decreased urinary Na excretion and increased the plasma aldosterone concentration and water retention before the onset of increased blood pressure. These findings suggest that the increase in the blood pressure in these rats might be the result of the same mechanisms as in the rats treated with Cd alone. Se administered simultaneously with Cd ameliorates the Cd-induced decrease in blood pressure on days 3 and 8 but did not ameliorate the Cd-induced increase in blood pressure on day 26. The Cd concentration in the serum of rats treated with Cd and Se simultaneously was markedly higher than that in the serum of rats treated with Cd alone on day 3, suggesting that a Cd−Se complex in serum would be formed. The effect of Se in preventing a Cd-induced decrease in blood pressure may be associated with the formation of a Cd-Se complex in the serum on day 3. On the other hand, after termination of treatment with Cd and Se there was no significant difference in the Cd concentrations in the serum between the rats treated with Cd alone and the rats treated with Cd and Se together. These findings suggest that a Cd−Se complex formed in serum on day 3 might be dissociated by day 26.