The association between isolation of the syncytium-inducing (SI) phenotype of human immunodeficiency virus (HIV) and unfavorable clinical and immune status was evaluated in a cross-sectional study. Data on HIV phenotype were available for 341 of 878 persons entering clinical trials of antiretroviral therapies. Patients with SI virus were demographically similar to those with non-SI (NSI) virus but were more likely to have a diagnosis of AIDS and detectable circulating HIV p24 antigen. Patients with SI virus also had a lower CD4+ cell count and a higher serum level of beta 2-microglobulin. The association between phenotype and present status was explained statistically by CD4+ cell count. Phenotype, serum level of beta 2-microglobulin, and the presence of detectable p24 antigen were all independent predictors of present CD4+ cell count. The likelihood of finding SI virus increased with unfavorable virologic and immunologic parameters and varied with the amount of prior antiretroviral therapy.