Human biopsies obtained from skeletal muscle of cachectic AIDS patients clearly showed an increased expression (in relation to that of healthy subjects) of the genes encoding for the ubiquitin-ATP-dependent proteolytic system. Increases of 120% and 42% were observed for the 2.4 and 1.2 kb ubiquitin transcripts, respectively. The expression of the C8 proteasome subunit was also increased by 60% in the cachectic AIDS patients in relation to the healthy control subjects. It is suggested that the activation of this proteolytic system (possibly via changes in circulating cytokines, such as TNF) may be responsible for the skeletal muscle waste that often accompanies AIDS.