Lymphocytic choriomeningitis virus (LCMV) may cause a severe immunosuppression in mice. Its pathogenesis is apparently dependent on LCMV‐specific CD8 effector T cells that mediate the destruction of virus‐infected cells which are normally essentially involved in immune responses. Evaluation of various LCMV isolates in this study established a general correlation between their tropism for lymphohemopoietic cells and immunosuppression. When immune responses were assessed as the capacity of mice to mount an anti‐vaccinia virus cytotoxic T cell response or an IgG response to vesicular stomatitis virus (VSV), after a primary LCMV infection, LCMV‐Armstrong, WE, Clone 13 and Docile were increasingly immunosuppressive in a dose‐dependent fashion with respect to both extent and duration. Analysis of lymphocyte subpopulations showed variable effects of the various LCMV isolates that did not reveal patterns readily explaining immunosuppression. To evaluate whether LCMV infection affected T and/or B cell functions directly or whether antigen presentation was impaired, adoptive transfer experiments were performed. Untreated or irradiated but uninfected normal recipient mice receiving adoptively transferred T or B cells from LCMV‐WE or Docile‐infected immunosuppressed donor mice responded within 30%–100% of normal ranges in both assay systems. In contrast, when T or B cells from normal donors were transferred to irradiated or non‐irradiated LCMV‐immunosuppressed recipients, they failed to mount a significant cytotoxic T cell response against vaccinia virus or an IgG response to VSV. Thus, the T and B cells from LCMV‐immunosuppressed mice were able to function within normal ranges; in contrast, histologically and functionally, antigen presentation was severely impaired in LCMV‐immunosuppressed mice.