A transregulatory gene, trs, of human immunodeficiency virus I (HIV-1) was expressed in bacteria as a 26-kD fusion protein. Survey of over 100 individuals infected with HIV revealed a nonrandom distribution of seropositivity against trs: a few of the asymptomatic carriers and AIDS patients (less than 5%) had sera that reacted with the 26-kD protein. In contrast, 29% of the ARC patients' sera reacted positively. This result is different from those of serological reactivities of the other accessory gene products of HIV-1 (tat, sor, 3' orf, and R) which did not differentiate among stages of clinical progression. Since ARC is a prodrome for full-blown AIDS, these results suggest that trs may be useful as a prognostic marker for AIDS development.