Continuous application of norepinephrine (NE) in rats has been shown to elevate early interleukin (IL)-6 mRNA expression in myocyte (MC) and nonmyocyte (NMC) cell fraction. The expression of IL 6 was also elevated in isolated rat MC and fibroblasts by NE treatment. Isoproterenol (Iso) elevated the expression of IL-6 only in fibroblasts and not in MC isolated from mouse heart. Therefore, we tested the hypothesis that NE-induced IL-6 elevation in MC is due to a adrenergic receptor stimulation and that NE-induced elevation in NMC is due to b receptor stimulation. Iso (1.25 mg/kg per h), phenylephrine (PE, 1.25 mg/kg per h) or the combination of both was given subcutaneously for 4 h in male BALB/c mice. Sham operated animals served as controls. Freshly obtained ventricular myocardium was dissociated into MC and NMC fractions. IL-6 mRNA, detected by ribonuclease protection assay, was elevated to the same extent in MC and NMC by the combination of Iso and PE (23- and 18-fold, respectively). b-Adrenergic stimulation by Iso induced higher IL-6 expression in MC than in NMC (7.6- and 2.9-fold, respectively). a-Adrenergic stimulation by PE did not stimulate IL 6 expression in MC nor in NMC. Thus there might be a crosstalk between a- and b-adrenergic receptors, since combined receptor stimulation elevated IL-6 expression to a greater extent than b-adrenergic stimulation alone.