As agencies develop guidelines for administering the newly developed hepatitis A virus (HAV) vaccine, information is needed regarding the occurrence of HAV infection in groups putatively at risk for the infection. We tested serum samples from 300 injection drug users (IDUs), 300 homosexual males, and 300 blood donors for the presence of total antibody to HAV (anti-HAV). Anti-HAV was detected in 66% of IDUs, 32% of homosexual males, and 14% of blood donors. Anti-HAV was not significantly associated (P > .10) with high-risk drug-using behaviors but was more prevalent among IDUs with annual incomes of <$5,000 (P = .018). The occurrence of anti-HAV increased among homosexual males as the number of sexual partners increased (P < .001) but was similar to the age-adjusted prevalence (30.6%) estimated for the general United States population. IDUs are at increased risk for HAV infection; however, our data suggest that factors related to low socioeconomic status contribute more to the occurrence of HAV infection among IDUs than does injection drug use. IDUs and persons at risk for injection drug use should receive HAV vaccine.