Anti-nuclear antibodies (ANA) in serum were detected in male ICR mice fed drinking water containing 3, 30 and 300 ppm Cd as CdCl2 for 10 weeks. In response to Cd exposure, ICR mice developed ANA of the IgG class giving nuclear patterns moderately stained by immunofluorescence or immunoenzyme method. Positive immunofluorescence staining of ANA was obtained in 50, 89 and 90% of ICR mice exposed to 3, 30 and 300 ppm Cd, respectively. Their spleen cells also showed an enhancement of antibody forming response to sheep red blood cells (SRBC) without the SRBC priming. When mice were primed with SRBC after exposure to Cd, however, a significant suppression of the antibody forming response was observed in mice fed 300 ppm Cd but not in those fed 3 ppm Cd. No significant differences in delayed-type hypersensitivity reaction to SRBC were observed between Cd-fed and control animals. Inbred BALB/c mice were less susceptible to the induction of ANA by Cd, as induced only in 300 ppm Cd-fed mice. Thus environmental exposure to Cd can induce ANA in ICR mice with a high susceptibility, presumably accompanied with a non-specific stimulation of antibody formation.