The extensive effort made to comprehend the complex immunopathology of human immunodeficiency virus (HIV) infection has resulted in research groups focusing attention on hypotheses as disparate as the possible 'superantigen' potential of HIV and the possible requirement for a Mycoplasma 'cofactor'. Utilizing the recent observation that a Mycoplasma species possesses 'superantigen' properties, this paper attempts to reconcile these seemingly discrepant observations in a model of the acquired immunodeficiency syndrome (AIDS) which builds on the potential contribution of a 'superantigen cofactor' to the ongoing process of HIV infection. A possible role for mycoplasma-induced T-cell proliferation, T-cell dysfunction, B-cell proliferation, and hyperglobulinaemia in the exacerbation of HIV infection is discussed. The relevance of a recent observation regarding protein sequence homology between the mycoplasma adhesin protein and several human class II major histocompatibility complex (MHC) proteins is also examined and incorporated into this model.