Thin section electron microscopy was used to investigate cellular changes associated with the replication of rubella virus (RV) in Vero cells and to compare these changes to those of the related alphavirus, Semliki Forest virus (SFV). Conspicuous membrane-bound cytoplasmic vacuoles analogous to the alphavirus replication complexes were observed in RV infected cells but not in mock infected cells. The vacuoles were characterised by membrane-bound vesicles measuring about 60 nm which often displayed an irregular dense core and/or a network of fibres. These vesicles were morphologically distinct from RV particles and were generally located at regular intervals on the inner side of the surrounding membrane of the RV replication complex. Degenerating cellular material was often found in the membrane-bound vacuole of a replication complex. The replication complexes were intimately associated with the rough endoplasmic reticulum (RER), which was localised 45–75 nm from the surrounding membrane of the replication complex. Parallel studies of replication complexes in SFV infected cells did not reveal such an intimate association with the RER. RV replication complexes appeared as early as 8 h post infection (p.i.), before detection of RV particles by electron microscopy, and their peak production at 24 h p.i. coincided with the time of maximum virus titre.