The oral absorption of cyclosporin A (CyA) was studied in rats after 6, 12, 18, and 23 mg kg-1 doses were given in an olive oil solution to determine if CyA absorption from the gastrointestinal tract was dose-dependent. Using serial blood samples obtained at various times after the respective doses, analysis of the resultant blood CyA concentration-time curves suggested that the rate of CyA absorption for all four doses was an apparent zero-order process. Moreover, the rate of CyA absorption appeared to be dose-dependent, increasing as the dose of CyA increased. Similarly, the extent of CyA absorption (F) also exhibited dose-dependent characteristics in this study. F increased from 0.13 after the 6 mg kg-1 dose to 0.22 with the 18 and 23 mg kg-1 doses (p less than 0.05). In the present investigation, the observed values for the duration of drug absorption (T), terminal first-order rate constant (beta) and corresponding elimination half-life (T 1/2 beta) of approximately 4-5 h, 0.030 h-1 and 21-28 h, respectively, were similar for all CyA doses. Moreover, no difference in beta was observed after oral or intravenous drug administration. Absorption lag times of 1-2 h were found. The results suggested that the dose-dependent absorption of CyA observed in the present study was possibly related to the effects of olive oil on gastric emptying and that CyA might be unstable in the gastric fluids and/or metabolized by the gastric mucosa.