Hypoxia is an important challenge for newborn mammals. Stress generated at the brain level under low oxygenation conditions results in up-regulation of heat shock proteins (HSPs) and other stress proteins. The aim of the present work was to determine the effect of hypoxia in the newborn on some newly described small molecular weight HSPs (HSP 20 and B8) in the hippocampus, cortex and cerebellum of newborn piglets. These effects will be compared with those of other closely related proteins such as alphaB crystallin, HSP 27, heme oxygenase (HO)-1, HO-2, cyclooxygenase (COX)-1 and COX-2. The piglets were submitted to hypoxia (5% O(2); 95% N(2)) over either 1 or 4 h, with recovery periods ranging from 0 to 68 h. Western blot analysis showed that HSP 20 was rapidly induced only in the hippocampus, long before hypoxia-inducible transcription factor HIF-1alpha, while HSP 27 was rapidly induced in the cortex and cerebellum. Vascular epithelial growth factor was increased simultaneously in the three regions. Moreover, an increase in the expression of, respectively, HO-1 and COX-2 was observed later, but at the same time, in the three regions tested. It appears that HSP 20 can be an early marker of hypoxia in the hippocampus. The other small HSPs or stress proteins display different temporal patterns of up-regulation (HSP 27 and HO-1, COX-2) or do not show changes in their expressions (alphaB crystallin, HSP B8, HO-2 and COX-1).