Background: Ultraviolet light (UVL) upregulates HIV transcription in vitro and in transgenic mice. AIDS-associated psoriasis and pruritus respond to phototherapy. Objective: Our goal was to determine the effect of phototherapy on viral load and immunologic parameters in HIV-positive patients. Methods: T cell subsets, p24, plasma cytokines, serum or plasma HIV-RNA, dosage, and antivirals were assessed in HIV-positive patients and negative controls receiving 6 weeks of phototherapy with UVB and in untreated controls. Results: Phototherapy improved skin conditions without significantly affecting T cell numbers. Plasma p24 increased 2-fold (P = .055) and HIV-RNA levels 4-fold (P = .022) 6 weeks from baseline in patients who entered the trial before March 1995. Later patients who were mostly receiving combination antiviral therapy showed a 4-fold reduction in serum HIV-RNA (P = .012) at 2 weeks. The effect of UVB on viral load at 6 weeks was dependent on the baseline level (P = .006). IL-10 increased and was inversely related to HIV-RNA levels (P = .0267). Conclusion: Phototherapy is associated with HIV load alterations, depending on patients’ initial HIV-RNA, antiviral therapy, skin type, and UVL dosage. (J Am Acad Dermatol 1999;40:48-60.)