The purpose of the present study was to examine the effect of social isolation stress on the expression of messengers ribonucleic acid (mRNAs) for corticotropin-releasing factor receptor type 2 (CRF 2 receptor), urocortin 1 (Ucn 1) and urocortin 2 (Ucn 2) in the cardiovascular system of female and male prairie voles ( Microtus ochrogaster). Isolation for 1 h (single isolation) or 1 h of isolation every day for 4 weeks (repeated isolation) was followed by a marked increase in plasma corticosterone level. However, continuous isolation for 4 weeks (chronic isolation) did not significantly affect plasma corticosterone level in female or male animals. A single period of isolation did not influence the expression of the CRF 2 receptor, however, both repeated and chronic isolation significantly decreased CRF 2 receptor mRNA in the ventricle and aorta of both sexes. Neither single nor chronic isolation significantly affected Ucn 1 mRNAs expression; however, repeated isolation increased Ucn 1 mRNA expression in the ventricles of female and male animals. Although, a single isolation produced no effect on cardiac Ucn 2 mRNA expression, both repeated and chronic isolation were followed by increased heart Ucn 2 mRNA expression in both sexes. We speculate that during repeated isolation Ucn 1 along with Ucn 2 are increased, which in turn down-regulates CRF 2 receptor mRNA expression, and that Ucn 2 also may be one of factors responsible for the down-regulation of CRF 2 receptor mRNA expression in cardiovascular system that is associated with chronic isolation.