The present study assesses the relationships among ED50 to neuroleptic-induced catalepsy and regional brain D1 and D2 dopamine receptor binding for eight inbred strains of mice (A, AKR, BALB/c, C3H, C57BL/6, CBA, DBA/2 and LP). The ED50 for haloperidol among these strains varies 30-fold from the most sensitive (BALB/c 0.31 mg/kg) to least sensitive (LP 9.5 mg/kg). As measured by quantitative receptor autoradiography, the haloperidol ED50 shows a significant positive correlation with [3H]spiroperidol binding to somatodendritic autoreceptors in the midbrain dopamine cell groups (A8, A9 and A10), but not with binding in the striatum. Although there are strain differences in [3H]SCH23390 binding in all regions studied, D1 receptor density was not correlated with haloperidol ED50. Within the striatum of these eight strains, there is no correlation between [3H]spiroperidol binding and [3H]SCH23390 binding. Overall, these data indicate that sensitivity to neuroleptic induced catalepsy is a genetically determined trait and that midbrain D2 receptor density may contribute significantly to the variance in this response.