Immune complex formation and immune virolysis of the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) were examined. LCMV, harvested from acutely infected BHK cells propagated in the absence of serum, was purified by methanol precipitation and sucrose density gradient centrifugation. The 31- and 23-S RNA species of LCMV were labeled under conditions of actinomycin D treatment of cells that prevented the labeling of cell ribosomes in the virion. The addition of guinea pig antibody (Ab) to LCMV lowered viral infectivity and enhanced the sedimentation rate but not the density of [U-³H]LCMV and ¹²⁵iodine-surface protein-labeled LCMV. This suggested that Ab aggregated the virions into faster sedimenting complexes. The addition of complement (C) to the LCMV-Ab complex further reduced the infectivity and increased both the sedimentation rate and density of [¹²⁵I]LCMV. When [U-³H]LCMV was reacted with Ab and C and subjected to rate zonal sedimentation, the RNA label remained at the top of the gradient rather than sedimenting with the ¹²⁵I-surface protein-membrane label. This observation, which indicated that Ab and C lysed the virus, was confirmed by electron microscopy showing first coating of the viral membrane with electron dense material, then swelling and rupture of the membrane and release of viral core material. Using sera deficient in specified C components, it was found that the C-mediated inactivation proceeded via the classical C pathway. Sera deficient in latter C components (beyond C3) augmented the inactivation of LCMV-Ab complexes, but this inactivation was far more extensive when a complete C source was used. Evidence suggesting that immune and persistently infected mice produce C-fixing Ab to the surface of the LCM virion was documented.