To test the hypothesis that whole-body heat acclimation (HA) would increase peripheral blood mononuclear cells' (PBMC) tolerance to heat shock (HS) and/or alter the release of cytokines (IL-1ÃŸ, IL-6, IL-10 and TNF-') to bacterial lipopolysaccharide (LPS), we heat acclimated nine subjects by exercising them for 100Â min in a hot environment for 10Â days. The subjects' PBMC were separated and cultured on days 1 and 10 of HA pre- and post-exercise. Pre-exercise PBMC were allocated to three treatments: control (PRE, 37°C), HS (42.5°C for 2Â h), or LPS (1Â ngÂ mL'1 for 24Â h). Post-exercise samples were incubated at 37°C. PBMC lactate dehydrogenase release increased (pÂ <Â 0.05) after HS but it was not different (pÂ >Â 0.05) between days 1 and 10 (0.100Â ±Â 0.012 and 0.102Â ±Â 0.16 abs., respectively). LPS treatment induced an increased (pÂ <Â 0.05) release of cytokines but HA did not alter this response (pÂ >Â 0.05). Pre-exercise intracellular heat shock protein 72 (Hsp72) was higher (pÂ <Â 0.05) on day 10 compared to day 1 of HA (13Â ±Â 5 and 8Â ±Â 5Â ngÂ mL'1, respectively). HS treatment caused a greater increase (pÂ <Â 0.05) in Hsp72 than the exercise sessions on HA days 1 and 10. In addition, after HA, the Hsp72 response to HS was reduced (day 1, 129Â ±Â 46; day 10, 80Â ±Â 32Â ngÂ mL'1, pÂ <Â 0.05). In conclusion, HA increases PBMC Hsp72 but it does not reduce cellular damage to HS or alter cytokine response to LPS. We speculate that the stress applied during HA is not sufficient to modify the PBMC response.