The purpose of this study was to determine whether testosterone replacement therapy ameliorates sexual dysfunction and associated problems of mood, energy, and appetite in HIV+ men with immune suppression (CD4 < 400 cells/cu mm) and low levels of serum testosterone. Assessments at study baseline and endpoint included psychiatric evaluation using the Structured Clinical Interview for DSM-III-R, the Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, the Karnofsky Performance Index, and a side-effects rating scale. Eighty-one men entered treatment and 72 completed at least 8 weeks. At study entry, 84% had an AIDS-defining condition (1993 CDC Criteria). In terms of sexual interest and function, 85% of study completers were clearcut responders at week 8. Mood response was also good: of the 44 study completers who had mood problems at baseline, 28 (64%) were rated as much improved. Mean change in CD4 cell count after treatment was not statistically significant. These findings suggest that testosterone replacement therapy should be considered for men with immune suppression and low testosterone levels who complain of diminished sexual desire and/or dysfunction. Replication with a placebo component is indicated.