Viruses remain one of the inducers of the stress response in the infected cells. Heat shock response induced by Moscow strain of ectromelia (mousepox) virus (ECTV-MOS) was studied in vitro in mouse monocyte cell line, RAW 264.7 and in vivo in BALB/c (H-2d) mice. In our studies we found that ECTV-MOS-infected RAW 264.7 cells up-regulated hsp-70 and hsp-90 expression during the phase of intensive virus replication in vitro. In spleen, lymph nodes (DLN) and liver of BALB/c mice inoculated with ECTV-MOS, virus replication was not accompanied by apoptosis of macrophages identified as CD11b+ cells and high loads of CD11b+/ECTV-MOS+ cells could be detected. Intensive virus replication in the spleen and lymph nodes was accompanied with elevated expression of hsp-27, hsp-70, and hsp-90. Particularly, CD11b+ cells showed up-regulation of hsp-27 (spleen, lymph nodes) and hsp-70 (spleen) at the peak of virus replication and up-regulation of hsp-90 during later stages of infection (15 and 20 day post infection). We conclude that during ECTV-MOS infection in vivo, hsps expressed by CD11b+ cells may play a dual role as anti-apoptotic factors fostering virus replication and as regulators of anti-viral response.