Intertidal zone organisms experience thermal stress during periods of low tide, and much work has shown that induction of heat shock proteins and ubiquitination occurs in response to this stress. However, less is known of other cellular pathways that are regulated following thermal stress in these organisms. Here, we used a functional genomics approach to identify genes that were up- and downregulated following heat stress in the intertidal porcelain crab, Petrolisthes cinctipes using custom cDNA microarrays made from 13,824 cloned P. cinctipes ESTs representing 6717 unique consensus sequences. Statistically significant differences in gene expression between heat stressed and control groups were determined with R/maanova. Genes upregulated following heat stress were involved with protein folding, protein degradation, protein synthesis and gluconeogenesis, suggesting that heat stress accelerated protein turnover. Genes downregulated following heat stress were involved with detoxification, oxygen transport, oxidative phosphorylation, and lipid metabolism, suggesting that the animals were avoiding the generation of reactive oxygen species. ESTs matching hypothetical proteins and ESTs that had no GenBank match were also found to have been both upregulated and downregulated following heat stress, suggesting that novel genes may be involved in the heat stress response.