Red blood cell parameters were assessed in a natural population of the northern red-backed vole (Clethrionomys rutilus Pallas, 1779) in the zone of influence of the Kirovgrad Copper Smelter along a gradient of pollution by heavy metals (Cu, Zn, Cd, and Pb) at three catching sites (polluted [Imp] and controls [Bg-1, and Bg-2]). The difference of the smelter area (Imp group of voles) from both background groups (Bg-1 and Bg-2) was proven by means of a set of 13 parameters in univariate and multivariate analyses. Among the detected erythrocyte disturbances, we noted the following: a decrease in activities of Na+,K+-ATPase and antioxidant enzymes (SOD, GSH-Px, and CAT); an increase in the concentration of lipid peroxidation products, in osmotic fragility, and in intravascular hemolysis; interruption of carbohydrate metabolism; and lowered oxygen-carrying capacity. A higher load of Cd (p = 0.0009) and possibly Pb (p = 0.054) in the Imp animals was confirmed by quantitation of heavy metals in the liver. Most erythrocyte parameters (11 out of 13) covaried with individual Cd load by obeying a semilogarithmic dependence; such a relation was not found for Cu, Zn, and Pb. A decrease in the growth rate of structural and functional erythrocyte aberrations ("resistance improvement") with increasing cadmium load is probably due to compensatory enhancement of the synthesis of metallothioneins in the liver and kidneys and hence a greater proportion of Cd bound to metallothioneins. Problems of differences/similarities in Cd-associated reactivity among the animals are discussed too, taking into account the catching sites (polluted [Imp] and controls [Bg-1, and Bg-2]) and reproductive-age (i.e., immature underyearlings, mature underyearlings, and individuals that overwintered). The persistence of differences in erythrocyte status observed by us between the Imp and background groups after normalization to Cd load may be due to the action of other (unexamined) adverse factors and calls for further ecotoxicological studies.