AbstractAsymmetric disulfide conjugates of mercaptosuccinyl tobacco mosaic virus (TMV ∼ SH) withNα‐desacetyl‐Nα‐5‐(mercaptovaleryl)‐α‐melanotropin were preparedviatheS‐sulfoderivative of the peptide. The conjugates, TMV ∼ SS ∼ α‐MSH(n), contained up ton= 330 disulfide‐linked peptide molecules/virion. Similarly, fluorescent conjugates, Rh(m) ∼ TMV ∼ SS ∼ α‐MSH(n) were prepared, containingm≈︁ 200 rhodamine molecules linked to the virions by thiourea bridges. Such conjugates were designed to study α‐MSH receptor localization and dynamics (mainly internalization), because the carrier virions which served to enhance specific receptor binding and as fluorescent or radioactive markers may be detached from the neuropeptides at will by reduction. Reduction occurred in solution and on the cell surface, but not in the cytoplasm, thus allowing detection of internalized agonist‐receptor complexes. The conjugates were superpotent agonists for tyrosinase stimulation inCloudman S‐91melanoma cell cultures, but were inactive forcyclicAMP accumulation. Their rather rapid internalization and the influence of reducing agents and other agonists on their biologic activity suggest a close connection between receptor location and biologic response as w