In contrast to a previous report (Fields M, Lewis C, Scholfield DJ, Powell AS, Rose AJ, Reiser S, Smith, JC. Proc Soc Exp Biol Med 183:145-149, 1986), female rats were shown to be susceptible to copper (Cu) deficiency giving rise to restriction of growth, cardiac hypertrophy, and anemia. The severity of these effects was, however, found to be less marked than in the male rats which had similar liver Cu levels. Castration or ovariectomy of Cu-deficient rats had little effect on CH or the other parameters associated with Cu deficiency, and supplementation of the neutered animals with estrogen or testosterone was similarly without effect. The ultrastructural appearance of the hypertrophied Cu-deficient female heart was similar to that previously found in males and was characterized by a large increase in mitochondrial area with disrupted cristae. The results also indicated that in contrast to Cu-deficient males iron (Fe) was not accumulated in the liver of the Cu-deficient female rats. It may be concluded that the limited protection of female rats to the effects of Cu deficiency observed in this study were unconnected with the sex steroids.