This paper presents an analysis of the protective properties of the components in ribonuclease (RNase)-sensitive ribosomal vaccines, in particular the ribonucleic acid (RNA). The protective activities in mice of purified ribosomes derived from Pseudomonas aeruginosa and from Listeria monocytogenes were compared. Both ribosomal vaccines had to be combined with the adjuvant dimethyldioctadecylammonium bromide (DDA) in order to be protective, and both lost their activity after RNase treatment. The ribosomal vaccines as well as RNA purified from the ribosomes induced non-specific protection. Intraperitoneal injection of RNA with DDA induced an influx of peritoneal cells. Furthermore, RNA with DDA activated macrophages as shown by, a.o., enhanced phagocytic activity and killing capacity for L. monocytogenes. The results suggest that the observed macrophage activation is probably T-cell-independent. With regard to the ribosomal vaccine of P. aeruginosa it is concluded that RNA also contributed to the protective activity by increasing the humoral response against suboptimal concentrations of contaminating cell surface antigens. In conclusion, it is proposed that ribosomal vaccines may be considered as a combination of a non-specific immunomodulator (RNA) with pathogen-specific cell surface antigens. This concept of ribosomal vaccines is discussed in relation to the literature concerning RNase-sensitive ribosomal vaccines.