Alterations in dopaminergic activity may play an important role in the pathogenesis of schizophrenia. The central effects of dopamine are mediated by at least five G protein-coupled receptors, Dl, D2, D3, D4 and D5. The Dl receptor maps to 5q35.1 and it identifies an Eco RI as well as a Taq I RFLP. In the present study we undertook a linkage analysis between the Dl receptor RFLPs and schizophrenia in 9 multigenerational families in which segregation of disease was consistent with autosomal dominant inheritance and reduced penetrance. Several flanking DNA markers were also analyzed as the Dl receptor RFLPs were relatively uninformative in our families. Pairwise analyses of schizophrenia and several flanking markers indicate that inheritability of this region is unlikely to be involved in the pathogenesis of schizophrenia in the 9 families studied.