Cyclosporine has been described to increase the sympathetic tone. Alterations in sympathetic tone may contribute to baroreceptor dysfunction. Therefore, in this study baroreceptor function in 20 kidney transplant recipients was investigated under both low and high cyclosporine whole blood concentrations using the sequence analysis technique. The sympathetic nerve activity was estimated by calculating the low frequency oscillation of heart rate and blood pressure following Fast Fourier Transformation (FFT). Besides cyclosporine, azathioprine and prednisolone no other drugs were used. The increase in cyclosporine whole blood levels (from 101+/-13.4 ng/ml to 469+/-52 ng/ml) did not change mean arterial blood pressure significantly (83.7+/-2.5 vs. 82.2+/-2.0 mm Hg). Baroreflex sensitivity in +PI/+RR (+pulsinterval/+blood pressure) sequences, however, increased from 11.2+/-0.4 to 13.0+/-0.5 ms/mm Hg, whereas it was reduced in -PI/-RR (-pulsinterval/-blood pressure) sequences (14.4+/-0.3 to 12.5+/-1.1 ms/mm Hg). The increase in cyclosporine whole blood concentrations was associated with an increase in low frequency oscillation of heart rate (430+/-12 to 461+/-13) and blood pressure (452+/-9 to 469+/-12), indicating an enhanced sympathetic tone. Our results provide evidence that cyclosporine A by itself alters baroreceptor function. An imbalance between the sympathetic and parasympathetic nervous system due to an enhanced sympathetic tone may explain the reduction in -PI/-RR and the increase in +PI/+RR sequence baroreflex sensitivity.