Spontaneous locomotor activity and dopaminergic responsivity were assessed after long-term dietary treatment with the anti-manic drug lithium. Chronic dietary Li administration was not accompanied by the toxicities often reported with other modes of administration. In addition, the diet reliably yields serum and brain Li levels in the prophylactic range for manic-depressive illness. After 4 weeks exposure to Li, spontaneous locomotor activity was reduced as compared to subjects on the control diet whether or not food intake was restricted. The depression of locomotor activity following an injection of the dopamine agonist, apomorphine, was less severe in animals that ingested Li compared to those with free access to the control diet. Finally, in confirmation of the findings of Pert et al., chronic Li administration led to a partial attenuation of apomorphine-evoked stereotyped behaviors in subjects rendered supersensitive to the drug by daily injections of haloperidol (HAL) for 3 weeks. The findings suggest that the commonly reported suppressant action of Li on spontaneous behavior is not attributable to overt toxicity or to diminished growth rate. Similarly, these health factors do not account for the ability of chronic Li treatment to suppress the behavioral manifestation of dopaminergic supersensitivity associated with long-term HAL exposure.