Soluble CD30 (sCD30) levels within 3 years of HIV seroconversion were studied in 85 hemophilic men infected with HIV. All men were coinfected with hepatitis C virus (HCV). Levels of sCD30 were elevated in these men when compared with controls. These elevated levels did not appear to be a result of treatment with intermediate-purity clotting factor concentrates and were unlikely to be due to HCV coinfection inasmuch as hemophilic patients infected with HCV alone showed only mildly elevated sCD30 levels when compared with those of hemophilic controls uninfected with HCV. Initial sCD30 levels were not significantly associated with progression to any endpoint, although a tendency was present for those with the highest initial levels to progress less rapidly than those with lower values. Despite elevated sCD30 levels in these men, we have not been able to confirm that high sCD30 levels are associated with more rapid HIV progression.