CEM15 (or APOBEC3G) has recently been identified as an inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. To evaluate the impact of its genetic variations on the progression of acquired immunodeficiency syndrome (AIDS), we have performed an extensive genetic analysis of CEM15. We have sequenced CEM15 in a cohort of 327 HIV-1-seropositive patients with extreme disease progression phenotypes--either slow progression or rapid progression--and in 446 healthy control subjects, all of white descent. We have identified 29 polymorphisms with allele frequencies >1%, 14 of which were newly characterized. There were no significant associations between the polymorphisms or haplotypes of CEM15 and a disease progression phenotype in our cohort.