Sea-caged cod are limited in their movements in the water column, and thus can be exposed to large seasonal ( approximately 0-20 degrees C) temperature fluctuations. To investigate the physiological response of Atlantic cod to summer-like increases in temperature, we exposed 10 degrees C acclimated juvenile cod to a graded thermal challenge (1 degrees C increase every 5 days) and measured: (1) plasma cortisol and glucose levels; (2) the respiratory burst activity of blood leukocytes; and (3) the expression of specific immune-related genes [MHC Class I, Interleukin-1beta (IL-1beta), beta2-microglobulin (beta2-M), Immunoglobulin M (IgM)-light (L) and -heavy (H) chains] in the blood using quantitative reverse transcription-polymerase chain reaction (QRT-PCR). The experiment was stopped at 19.1 degrees C, with 26.7% of the fish surviving to this point. Plasma glucose levels increased slightly at 16 and 18 degrees C (by 1.39- and 1.74-fold, respectively), in contrast, cortisol levels were elevated significantly (by 2.9-fold) at 16 degrees C but returned to control levels thereafter. The effect of increasing temperature on the expression of immune related genes in blood cells (leukocytes) was variable and depended on the gene of interest. The expression of IgM-H remained stable for the duration of the experiment. In contrast, IL-1beta expression was increased significantly (by approximately 25-fold) at 19 degrees C as compared to time-matched control fish, and changes in the expression of beta2-M, MHC Class I and IgM-L followed a pattern similar to that seen for cortisol: increasing at 16 degrees C (by 4.2-, 5.3- and 17-fold, respectively), but returning to pre-stress levels by 19 degrees C. Interestingly, increasing temperatures had no effect on respiratory burst activity. This study is the first to examine the effects of a chronic regimen of increasing temperature on the stress physiology and immunology of a marine teleost, and suggests that immune function is influenced by complex interactions between thermal effects and temperature-induced stress (elevated circulating cortisol levels).