Qualitative and quantitative differences in the heat-shock response in brain, gill, and striated muscle tissues of the fathead minnow (Pimephales promelas) were investigated. The maximum sublethal heat-shock temperature was 34 °C. The heat-shock proteins (hsps) induced, their biosynthetic rates, minimum temperatures required for induction, and maximum temperatures at which each tissue synthesized hsps were tissue specific. Six hsps were induced in gill tissue (100, 90, 78, 70, 68, and 60 kDa), four in muscle tissue (100, 90, 78, and 70 kDa), and three in brain tissue (90, 70, and 68 kDa). Minimum temperatures required for inducing the stress response in gill, muscle, and brain were 28, 31, and 32 °C, respectively. Maximum hsp synthesis and accumulation occurred at 33 °C for the brain and 34°C for muscle and gill. Synthesis and accumulation of hsps decreased to near pre-exposure levels in the brain at 34 °C. The fact that brain tissue synthesized the fewest hsps and had the lowest capacity for synthesis at the upper thermal limits of the organism supports the hypothesis that the central nervous system governs the thermal limits to survival in poikilotherms.