With the aim of correlating pyomyositis with HIV infection, we have carried out a case-control comparison of HIV seroprevalence among patients affected by pyomyositis and an age and sex-matched control group of healthy subjects. Over a one-year period, 35 patients with pyomyositis, 20 male and 15 female, mean age 28.31 years, were admitted to Dr Ambrosoli Memorial Hospital of Kalongo (Kitgum District, Northern Uganda). Among these patients, II were HIV-antibody-positive, with a seroprevalence of 31.42%. In the age and sex-matched control group of 35 healthy subjects, selected in the same period from volunteers admitted to the surgical ward for orthopaedic trauma, two were HIV-antibody-positive, with a seroprevalence of 5.71%. The matched analysis produced a Mantel-Haenszel matched odds ratio of 5.50 and a maximum likelihood estimate of OR (MLE) of 5.50 (exact 95% confidence limits for MLE = 1.20 < OR < 51.07). Among the II HIV-seropositive patients, 9 (81.8%) fulfilled the World Health Organization (WHO) clinical case definition (CCD) for AIDS, compared with I of twenty-four (4.1%) HIV-negatives. The chi-square test for difference in fulfilling the CCD for AIDS between patients with pyomyositis seropositive and seronegative gave a statistically significant result (P < 0.0001). The authors conclude that pyomyositis is a bacterial infection very significantly associated with HIV infection, to be considered a strong sign of stage III-IV of HIV disease.