Macrophages from murine bone marrow (strain C3Hf Bu/Kam) were cultured in vitro in L-cell conditioned medium. After 0, 2, 4, 6, 8 and 10 days, they were infected with a clinical strain of herpes simplex virus type 1 and the outcome followed morphologically, by phagocytic index, infectious virus yields, immunofluorescence, expression of Fc receptors and major histocompatibility complex (MHC) Class II antigens. At a multiplicity of infection of 1-5, little morphological difference was apparent between infected and uninfected cultures at early stages in vitro but marked changes occurred later with reduction in cell numbers in the infected cultures. Indirect immunofluorescence failed to detect cells expressing early viral antigens, and yields of infectious virus indicated that permissive infection was not taking place. While phagocytic index and Fc receptor expression did not change 24 hours post-infection, MHC Class II antigen expression was increased. Thus, although the bone marrow macrophages seem predominantly resistant to infection with HSV-1, they may be modified by the presence of the virus. Since macrophages may act as antigen presenting cells for the immune system, this type of mechanism may be important in the generation of local immune responses.