Opioid receptors (OR) provide primary interaction sites of the human brain with opiates. Presently kappa-OR mRNA expression was studied in different cortical areas (A4, A10, A17) by in situ hybridization using digoxigenin-labeled oligonucleotides and an alkaline phosphatase-mediated color reaction. kappa-OR mRNA was expressed mainly in layers II/III and V pyramidal and layer VI multiform neurons. A4 giant pyramidal and A17 giant stellate neurons stood out labeled. These findings fit in with our data on kappa-OR protein distribution. Combined cellular assessment of protein and mRNA will enable the study kappa-OR expression under physiological and pathological conditions.