Barophilic growth of the hyperthermophilic methanarchaeon Methanocaldococcus jannaschii occurred when gas-substrate availability did not limit growth. In contrast, when growth was limited by gas transfer, no enhancement of growth was evident and a stress response was exhibited at both high and low pressure. A pressure-induced transcriptional response was evident, regardless of whether growth was enhanced by pressure. Potential high-pressure adaptation of a barophilic organism can thus occur at the transcriptional level, even though the cells are stressed by low substrate availability and do not exhibit accelerated growth.