After human rhinovirus type 2 (HRV-2) attaches to HeLa cells, two types of subviral particles are formed which closely resemble particles produced in vitro by acid or heat. One type of particle contains RNA whereas the second sediments as an empty capsid and is RNA-deficient. Sodium dodecyl sulfate (SDS) at 10(-4) M inhibits the cell-mediated formation of these particles from HRV-2 virions and the ability of HRV-2 to form plaques, but it does not inhibit the formation of plaques by human rhinovirus 14 (HRV-14). SDS also stabilizes HRV-2 against inactivation by acid or heat to a much greater extent than it does HRV-14. In a similar manner, SDS protects against the acid inactivation of the subpopulation of HRV-2 natural top component particles which attach to virus-specific cellular receptors. This suggests that the loss of native properties of natural top component particles and of virion are related processes. The basis for this alteration and also its role in infection are discussed.