The aim of this investigation was to reveal the regulatory properties of bacteriophage preparations in a model of mitogen-induced splenocyte proliferation in mice. We showed that sepharose 4B-purified preparations of the Staphylococcus aureus phage A20/R exhibited costimulatory activity in splenocyte proliferation induced by suboptimal (0.25 microg/ml) concentrations of ConA. On the other hand, the purified phage fraction was regulatory with regard to splenocyte proliferation induced by the optimal (2.5 microg/ml) ConA concentration. We also showed that the phage preparation can elicit IL-6 production in splenocyte cultures and enhance ConA-induced production of that cytokine. Furthermore, the phages preferentially induced IL-6 production in adherent splenocytes and increased levels of that cytokine in cultures of peritoneal cells from mice and rats. This phenomenon may explain the costimulatory activity of phages in the model described.