Do mathematical models contribute to immunology?

The ultimate aspiration of a theoretical biologist is to influence the thinking and work of experimental biologists and clinicians in a constructive way. Mostly, theoretical modeling in immunology has had a negligible impact. The grounds for this predicament are considered. Another commentator's warning, that a model unlinked to a viable conceptual framework is (at best) of marginal interest, is recalled. One recent exception is the surge of interest in mathematical models related to HIV infection and AIDS. Some models are critically reviewed. Finally, the difference between direct transmission of HIV in the infected tissues vs. cross-infection, and the significance of different modes of lymphocyte activation, are considered in a qualitative way. (C) 2000 Elsevier Science Ltd.