Early and late primary IgM antibody responses of mice to Thy-l.1 antigens showed different antigenic and cellular requirements. We studied genetic controls of the early primary responses, which could be induced by subcellular thymocyte antigens independently of host T-cell activity. All Thy-1.2 mouse strains of Igh ~ (BALB/c and BC8), Igh-VaC b (BAB14), Igh ~ (AKR/Cum), Igh ~ (CBA/J, C3H/HeN, C3H.SW, and C3H.JK), and Igh n (NZB) definitely responded early to Thy-l.1 antigens from AKR/J (Ighd), A.Thy-l.1 (Ighe), or B10.Thy-l.1 (Igh b) mice or SD rats, whereas all strains of Igh b (C57BL/6, C57BL/10, B 10.D2, B 10.BR, B10.A, CB20 and CWB), Igh C (DBA/2), Igh e (A/J), and Igh Β° (C.AL20) responded poorly to the same antigens. This contrasts with the observation that both strains of Igh j (C3H/HeN) and Igh b (B10.BR) responded well at later times. As was the case for late responses, the matching of H-2 between donor and recipient resulted in early responses of exceptional quality in high-responder strains. It was concluded that under the influence of H-2, whose incompatibility between donor and recipient partially interferes with responses, early but not late primary Thy-l.l-specific antibody responses are selectively controlled by Igh-Vor closely linked Ir gene(s) as a new V H marker.