We attempted to determine the effects of cyclosporine on beta-adrenergic receptors in bovine pulmonary artery smooth muscle cells. Bovine pulmonary artery smooth muscle cells were exposed to cyclosporine at a concentration of 100 ng/ml in culture media for 5 days, and control bovine pulmonary artery smooth muscle cells were exposed to only culture media for the same 5-day period. Beta-adrenergic receptors were measured as total binding capacity (Bmax) by nonlinear least squares fit of the specific binding curve. In a separate experiment beta1- versus beta2-adrenergic receptor subtypes were identified by computer modeling (LIGAND) of 17-19 point CGP20712A-125ICYP competition curves. Cyclosporine significantly (p=0.02) decreased bovine pulmonary artery smooth muscle beta-adrenergic receptor density by 54%+/-7%. The Bmax for control versus treated cells was 38.9+/-18 versus 17.7+/-12 fmol/mg protein, respectively. Subtype determination of beta-receptors revealed 70% or more beta2- and 30% or less beta1-adrenergic receptors. Cyclosporine caused a 54% reduction in overall beta-adrenergic receptor density in bovine pulmonary artery smooth muscle cells. The reduction in Bmax is suspected not to be a result of selective down-regulation of beta1-adrenergic receptors alone. We believe that cyclosporine may also contribute to a decrease in beta2-adrenergic receptors.