Unstimulated normal leukocytes were studied for their expression of corticotrophin-releasing factor (CRF)-like mRNA and peptide. In situ hybridization demonstrated CRF mRNA in T and B lymphocytes and in neutrophils. Northern blot analysis also detected the presence of a CRF mRNA species of approximately 1.7 Kb from lymphocytes and a peptide that reacted with anti-CRF antiserum was also detected by radioimmunoassay. This lymphocyte-derived peptide eluted earlier than standard CRF on high performance liquid chromatography. These findings suggest that regulatory mechanisms within the hypothalamus and the immune system may utilize closely related peptides.