Recombinant RNA based on the Semliki Forest virus (SFV) replicon was used to express the nucleoprotein of influenza virus in mice. Two strategies were employed to deliver the RNA. In the first, recombinant RNA was packaged into infectious suicide SFV particles which were used directly for immunization. The second approach involved injection of in vitro-synthesized RNA directly into the quadriceps muscle. Both approaches resulted in the generation of humoral responses with high antibody titres. Immunization with suicide particles showed that a strong, class I-restricted cytotoxic T-cell response can be obtained using only 100 infectious units. We conclude that the self-replicative recombinant SFV RNA may be quite useful as a nucleic acid vaccine.