We conducted anti-HIV testing on follow-up samples obtained at a mean interval of 20 weeks from 150 blood donors who had previously tested anti-HIV ELISA positive and Western blot atypical. Of 93 donors who demonstrated reactivity to HIV core protein p24, 4 progressed to positive Western blots. Most of the remaining donors showed a persistent p24 reactivity on Western blot and had no risk factors for HIV infection. Immunofluorescence testing of the initial sample from 93 donors could not definitively separate seroconverters from those with persistent p24 reactivity. Of 57 donors with p18 reactivity, none were positive on follow-up anti-HIV testing. Our findings suggest policies and strategies for notifying donors of atypical anti-HIV Western blot results.