Binding of 125I-iodohydroxybenzylpindolol to β-adrenoceptors has been examined in lymphoblastoid cell lines from members of 5 families affected by manic-depressive disorder. Cell lines from 6 manic-depressives, 7 unaffected relatives and 11 non-psychiatric controls were examined. Binding was reduced to less than half of control values in cell lines from 4 out of 6 manic-depressives and only 1 out of 18 unaffected relatives or controls. All the cell lines with reduced β-adrenoceptor binding came from 3 families; members of the remaining 2 families showed normal binding. These findings suggest that genetic heterogeneity is present in manic-depressive disorder and that a β-adrenoceptor defect may influence genetic susceptibility to the disorder.