Abstract The mechanisms involved in the neutralization of infectious equine arteritis virus (EAV)-antibody complexes by complement or anti-IgG serum were investigated. Analysis of label release from 3 H-uridine labeled RNA revealed that after addition of equine or guinea pig complement to sensitized EAV, disruption of the virion with release of RNase-sensitive viral RNA occurred within 30 min at 37 °. In contrast, when sensitized EAV was neutralized with either anti-IgG serum at 37 ° or complement at +2 °, the RNA label remained sedimentable and RNase-resistant. These data and studies with infectivity restored to complement-neutralized EAV-antibody complexes by trypsin treatment seemed to indicate that neutralization of infectious virus-antibody complexes precedes virolysis and takes place by steric hindrance of “critical sites” on the viral envelope. Complement-mediated neutralization is then followed by a temperature-sensitive step, possibly involving late-acting members of the complement series, which leads to virolysis.