Goalpha is a guanine nucloetide-binding regulatory protein alpha subunit which is mainly distributed in the central nervous system, but it has not previously been reported how it is regulated by thyroid hormone in the brain of neonatal rat at transcriptional levels. In this report, we used quantitative competitive reverse transcriptional PCR to quantify the effects of TH deficiency on Goalpha gene expression in the brain of neonatal rat at mRNA levels. It was found that Goalpha mRNA levels in the brain of 14-day-old rats significantly increased over 3-fold after induction of perinatal hypothyroidism, and declined markedly after treatment of thyroxine replacement. In situ hybridization histochemistry was further employed to observe the time-course and spatial expression of Goalpha gene in the brain of neonatal rats affected by thyroid hormone deficiency during the developmental period. The data showed that perinatal hypothyroidism can enhance Goalpha mRNA levels in the temporal cortex, sensorimotor cortex, piriform cortex, amygdala, hippocampal CA1-4 subfields, dentate gyrus, arcuate nucleus (AR) and ventromedial hypothalamic nucleus (VMH) of hypothalamus, but not in the striate cortex, cingulate cortex, claustrum, caudate/putamen and thalamus in the brain of rat at 7-21 days post-partum. The results suggest that up-regulation of Goalpha gene expression may be one kind of common mechanism responsible for neurological deficits in some brain areas arising from thyroid hormone deficiency in the critical periods of neonatal rats.