In fibroblasts, serum stimulation has been shown to activate the immediate-early gene 3CH134 encoding a dual specificity protein phosphatase that regulates mitogen-activated protein kinase. We report here that 3CH134 messenger RNA levels increase during recirculation following 30 min forebrain ischemia in the rat brain. In normal rat brains, 3CH134 messenger RNA was found mainly in neurons of the cortex and thalamus. At recirculation periods up to 1 h after 30 min ischemia, 3CH134 messenger RNA increased in neurons and glial cells of all previously ischemic brain regions. After 3 and 6 h recirculation, a prominent increase of 3CH134 messenger RNA was observed in the pyramidal cell layer of all sectors of the hippocampus and the granule cells of the dentate gyrus, whereas in the other brain regions messenger RNA levels returned to control. Up to 6 h of recirculation the spatial induction pattern of 3CH134 was similar to the pattern observed for the immediate-early genes c-fos and c-jun. Within the hippocampus a similar pattern was also observed for the heat shock protein hsp70 messenger RNA. At 12 and 24 h after ischemia, increased levels of 3CH134 messenger RNA persisted in hippocampal neurons; at the same time a delayed increase of 3CH134 messenger RNA was observed in large neurons of the thalamus and in glial cells in damaged regions of the striatum. At later survival periods, 3CH134 messenger RNA returned to control levels. Our study shows that the mitogen-activated protein kinase phosphatase 3CH134 is induced in the brain after a period of global ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)