The type of leprosy which develops after infection with Mycobacterium leprae is influenced by the presence or absence of HLA-DR3, as has been demonstrated in an ethnic group originating from Surinam. In the present study we investigated in this same ethnic group the role of HLA-DR, and of HLA-DR3 in particular, in monocyte-T cell interactions during leprosy specific proliferative responses in vitro. HLA-DR3 heterozygous T cells from tuberculoid leprosy patients were cultured with antigen and either HLA-DR3 positive or HLA-DR3 negative homozygous HLA-DR compatible allogeneic monocytes as antigen presenting cells (APCs). T cell proliferative responses with DR3 homozygous monocytes as APCs, were observed to be decreased as compared to T cell proliferative responses with DR3 negative homozygous monocytes as APCs. Furthermore, although the leprosy specific monocyte-T cell interactions were shown to be restricted for HLA-DR, in the anti-MLW-1 response HLA-DR3 appeared to function as a restricting element poorly or not at all. These observations may imply, that an in vitro correlate has been found for an (HLA associated) genetic control of leprosy in vivo.