Selective suppression of the immune system in graft recipients is now achieved in most cases by treatment with cyclosporine A. Due to large individual differences in absorption, utilization and metabolisation of this drug, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the cyclosporine concentrations in blood samples and dosage readjustments. In the present study, we measured cyclosporine in whole blood samples from 37 patients (23 liver and 14 heart transplant recipients) using an high pressure liquid chromatographic method for native cyclosporine A which has been developed in our laboratory and a radioimmunoassay method (cyclosporine A + metabolites). By comparison of the results of HPLC and RIA-measurements (n = 520) we found a relatively stable metabolization rate (RIA/HPLC-ratio) of 4.23 +/- 1.30 for heart transplant recipients. In contrast RIA/HPLC ratios were highly variable in liver graft recipients ranging from 1.3-9 for the same patient in the posttransplant period. The liver recipients could be classified into two groups according to their mean RIA/HPLC-ratios: for 11 patients we observed a mean ratio of 2.65 +/- 0.35, for another 12 patients one of 4.35 +/- 0.75. Lower metabolisation rates seem to be associated with low donor age. No direct correlation was found between changes in RIA/HPLC-ratios and liver function, rejection and infection periods. Rejection treatment with high doses of methylprednisolone had no systematic influence on cyclosporine metabolisation in our patients. Since cyclosporine metabolites, at least those ones which are most abundant, have less immunosuppressive and toxic effects we recommend measurements of cyclosporine blood concentrations with any HPLC-method specific for the unchanged drug.(ABSTRACT TRUNCATED AT 250 WORDS)