Cytotoxic T lymphocytes (CTL) specific for allelic products of minor histocompatibility locus, H-1, were generated in secondary in vitro cultures. Effector cells required H-2 compatibility between stimulates, responders, and target cells. There was no strict correlation between the strength of CTL respones to minor H antigens and the mean skin graft rejection times for these antigens. NZB mice respond to non-H-2 antigens after primary stimulation in vitro with H-2 compatible cells. The response is directed against H-2D-associated and Qa-1b-associated as well as other antigens. The response is controlled by two or more genes.