Background: Pruritic papular eruption (PPE) of HIV/AIDS is a common manifestation of HIV infection. Unfortunately, treatments for the unremitting pruritus have yielded only partial relief. Objective: Our purpose was to assess the clinical efficacy of pentoxifylline in the treatment of pruritus in HIV-infected patients with PPE while measuring its effects on HIV viral load and levels of serum triglycerides, tumor necrosis factor (TNF)–α, and interleukin (IL)-4. Methods: Eleven of the 12 patients with PPE and HIV infection placed on a regimen of oral pentoxifylline completed the 8-week study. The degree of pruritus both before and after therapy was measured by means of a patient-reported visual analog scale (0 = none and 10 = worst experienced). A global assessment of the number and size of PPE lesions was performed by the investigator, and serum TNF-α, IL-4, and triglyceride levels, as well as HIV viral load, were measured. Results: The average degree of pruritus was significantly reduced (p = 0.0009) from 6.5 at baseline examination to 3.6 at the end of the study. Ten of 11 patients experienced a reduction in their pruritus, ranging from 22.6% to 87.3%. The global assessment of PPE lesions decreased from baseline in most patients and increased slightly in one patient. Serum TNF-α was detectable in one patient at baseline, but was undetectable at the end of the study period. Similarly, the two patients who had detectable serum IL-4 at baseline had undetectable serum IL-4 levels at the end of the study. Triglyceride levels in six patients decreased an average of 23.9% by week 8. Although when compared with baseline values, HIV viral loads in seven patients decreased, one patient had no change, and three patients had an increase in their viral load at the end of the study, the magnitude of the changes were of little clinical importance. Conclusion: Pentoxifylline is a safe and efficacious treatment of pruritus in HIV-infected patients with PPE. Future controlled studies are needed to confirm the effectiveness of this treatment. (J Am Acad Dermatol 1998;38:955-9.)