Human immunodeficiency virus (HIV) isolability, rate of viral replication, HIV phenotype, type 1 and type 2 cytokine production, and CD4 counts were cross sectionally analyzed in 63 HIV seropositive (HIV+) individuals to establish possible correlations between virologic and immunologic markers of protection and progression. We observed that these markers are tightly correlated. Thus, lack or low prevalence of HIV isolability and the presence of nonsyncitium inducing strains are associated with the strongest type 1 cytokine production, the weakest type 2 cytokine production, and highest CD4 counts. Conversely, the isolation of highly replicating, syncitium-inducing HIV strains is associated with the weakest type 1 cytokine production, the strongest type 2 cytokine production, and lowest CD4 counts. Additionally, it was determined that the interleukin (IL)-10/IL-2 ratio best discriminates among different virologic scenarios. These data suggest that the virologic and immunologic correlates of disease protection and progression might be associated variables that define two different subsets of HIV+ individuals and lend support to a viro-immunologic hypothesis of HIV infection.