SummaryAn A/Sn × A.SW lymphoma (LNSF) and isoantigenic variants derived from it were studied with the use of monocomponent isoantisera in vitro. Representative antigens of 3 classes were analyzed: those derived from A/Sn alone (4, 8, 11), from A.SW alone (7, 19), and from both A/Sn and A.SW (3, 5). Variants were obtained from mice in which selection was directed against 4, 8, 11 (A.SW), 4 alone (A.SW × C3H), or 11 alone (A.SW × DBA/2). All variants retained A.SW antigens whether in A.SW alone or both A/Sn and A.SW. A.SW and A.SW × C3H variants lost 4, 8, 11. Four A.SW × DBA/2 variants were 4, 8, −11, while one was 4, −8, −11. The segregation of 8 in these variants indicated that 8 is between 4 and 11 in the H-2 chromosomal region, that a chromosomal alteration is most likely responsible for variant formation in vivo, and that this method can be used for genetic analysis of the H-2.