Administration of cyclosporine to allograft recipients and patients with immunologically mediated disorders is associated with a high incidence of the development of hypertension. We studied the effect of CsA on blood pressure and on the in vitro tail artery contractile response to transmural nerve stimulation (TNS) and exogenous norepinephrine (NE) in the spontaneously hypertensive rat (SHR). Fourteen days of p.o. administration of CsA 5 mg/kg/day (CsA5) or CsA 20 mg/kg/day (CsA20) resulted in significant increases in blood pressure. The effective level of TNS that resulted in a 50% of maximal response (ED50) was significantly (P < 0.05) decreased in the CsA5 and CsA20 animals compared to controls. The values for controls (n = 7), CsA5 (n = 10), and CsA20 (n = 9) were 4.3±0.3, 3.2±0.3, and 3.1±0.4 pulses/sec, respectively. In the CsA20 group, the doseresponse curve to NE was significantly shifted to the left, and the ED50was significantly (P< 0.01) decreased compared to controls (5.7 ± 0.8×10−5mol/L, n = 11, vs. 8.9±0.6×10−5mol/L, n = 12). We conclude that the in vitro contractile response to nerve stimulation is augmented by CsA. Some of the increase may be related to an enhancement of NE response, but a direct effect on neurovascular function is also suggested. This effect of CsA may be important in the development of hypertension and the changes in neurovascular tone seen with the clinical administration of this immunosuppressant.