Heat shock proteins (hsps) are a group of highly conserved proteins that represent between 2% and 15% of total cellular protein and are expressed by every living organism. The main functions of hsps are to regulate apoptosis and to act as intracellular molecular chaperones that facilitate protein folding and assembly. Some hsps are highly immunogenic and elicit humoral, cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell responses against viruses, tumors and infectious diseases. In the first study, twenty male patients with HIV disease and fifteen age-matched controls were recruited. Lymphocytes were isolated and incubated at either 37°C for 1 h or heat shocked at 42.5°C for 1 h. Lymphocytes were then allowed to recover at 37°C for 3 hand hsp expression was measured using both western immunoblots and 1D-SDS-PAGE (β-actin used as internal control). After a mild heat shock (from 37°C to 42.5°C for 1 hr) lymphocytes displayed an augmented synthesis of hsp 110, hsp 90 and hsp 70, relative to actin, in all individuals regardless of HIV-status. There were apparent differences in levels of expression of newly synthesized hsps between the HIV-positive and HIV-negative groups. Within this cohort these differences were not correlated with CD4+ count, viral load, dietary supplement use, smoking or the use of highly active antiretroviral therapy (HAART). The significance of altered hsp expression remains to be determined. However, given the recent reports on the role of these proteins in cross-presentation of antigens, α-defensin internalization and pro-inflammatory cytokine production, further investigation is merited.