The heavy chain variable portion of mouse myeloma protein MOPC‐315 (α, λ2) was obtained from its Fv fragment (J. Hochman, D. Inbar and D. Givol, Biochemistry 1973. 12: 1130.) and was used to immunize rabbits. Rabbit anti‐VH antibodies precipitated VH, Fv and the intact protein 315. The VH region specificity of these antibodies was evident from the line of identity in agar gel diffusion between Fv and M315, and from the lack of precipitation with another a chain of XRPC‐25 or with light (L) chains. Radioimmunoassay binding and inhibition studies demonstrated that anti‐VH 315 antibodies cross‐react with heavy (H) chains derived from various mouse myeloma proteins (MOPC‐460, XRPC‐25, MOPC‐104E, UPC‐10, TEPC‐15, HOPC‐8, MOPC‐167) as well as with H chains derived from mouse IgG. These H chains can inhibit 90–100% of the binding of VH 315 by anti‐VH indicating extensive sharing of antigenic determinants by various VH regions. The relative affinity of anti‐VH for various H chains was 20–1000‐fold weaker than its affinity for the MOPC‐315 H chain. The cross‐reaction of the various H chains was independent of antibody specificity, subclass, subgroup or CH allotype. This suggests that anti‐VH may be considered as anti‐V framework antibody. Anti‐VH 315 cross‐reacts with isolated H chains but not with intact molecules and can therefore be used to detect VH determinants only in the absence of chains.